Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

References

• Agache I, Palmer E, Sanver D, Kirtland M, Shamji MH. Molecular allergology approach to allergic asthma. Mol Aspects Med. 2022;85:101027.
   PubMed Web of Science ®Google Scholar
• Arteaga-Badillo DA, Portillo-Reyes J, Vargas-Mendoza N, et al. Asthma: new integrative treatment strategies for the next decades. Medicina. 2020;56:438.
   PubMedGoogle Scholar
• Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract. 2017;3:1.
   PubMedGoogle Scholar
• Guntur VP, Manka LA, Moore CM, et al. Refractory neutrophilic asthma and ciliary genes. J Allergy Clin Immunol. 2022;149:1970–1980.
   PubMed Web of Science ®Google Scholar
• Tong S, Yin Y, Bao Y. Climatotherapy for asthma: research progress and prospect. Environ Res. 2022;214:113988.
   PubMed Web of Science ®Google Scholar
• Liu J, Hong M, Li Y, Chen D, Wu Y, Hu Y. Programmed cell death tunes tumor immunity. Front Immunol. 2022;13:847345.
   PubMed Web of Science ®Google Scholar
• Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 2014;15:135–147.
   PubMed Web of Science ®Google Scholar
• Shi Z, Yuan S, Shi L, et al. Programmed cell death in spinal cord injury pathogenesis and therapy. Cell Prolif. 2021;54:e12992.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25:486–541.
   PubMed Web of Science ®Google Scholar
• Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–257.
   PubMed Web of Science ®Google Scholar
• Sauler M, Bazan IS, Lee PJ. Cell death in the lung: the apoptosis-necroptosis axis. Annu Rev Physiol. 2019;81:375–402.
   PubMed Web of Science ®Google Scholar
• Ketelut-Carneiro N, Fitzgerald KA. Apoptosis, pyroptosis, and necroptosis-oh my! The many ways a cell can die. J Mol Biol. 2022;434:167378.
   PubMed Web of Science ®Google Scholar
• Peña-Blanco A, García-Sáez AJ. Bax, Bak and beyond - mitochondrial performance in apoptosis. Febs j. 2018;285:416–431.
   PubMed Web of Science ®Google Scholar
• Ashkenazi A, Salvesen G. Regulated cell death: signaling and mechanisms. Annu Rev Cell Dev Biol. 2014;30:337–356.
   PubMed Web of Science ®Google Scholar
• Kashyap D, Garg VK, Goel N. Intrinsic and extrinsic pathways of apoptosis: role in cancer development and prognosis. Adv Protein Chem Struct Biol. 2021;125:73–120.
   PubMed Web of Science ®Google Scholar
• Santagostino SF, Assenmacher CA, Tarrant JC, Adedeji AO, Radaelli E. Mechanisms of regulated cell death: current perspectives. Vet Pathol. 2021;58:596–623.
   PubMed Web of Science ®Google Scholar
• Barros B, Almeida BR, Barros DTL, Toledo MS, Suzuki E. Respiratory epithelial cells: more than just a physical barrier to fungal infections. J Fungi. 2022;8:438.
   Web of Science ®Google Scholar
• Lloyd CM, Saglani S. Asthma and allergy: the emerging epithelium. Nat Med. 2010;16:273–274.
   PubMed Web of Science ®Google Scholar
• Martínez-Girón R, van Woerden HC. Disruption of airway epithelium in asthma pathogenesis: are protozoa responsible? Proc Am Thorac Soc. 2010;7:161.
   PubMedGoogle Scholar
• Chanez P. Severe asthma is an epithelial disease. Eur Respir J. 2005;25:945–946.
   PubMed Web of Science ®Google Scholar
• Truong-Tran AQ, Grosser D, Ruffin RE, Murgia C, Zalewski PD. Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation. Biochem Pharmacol. 2003;66:1459–1468.
   PubMed Web of Science ®Google Scholar
• Yamada Y, Yoshihara S, Arisaka O. Creola bodies in wheezing infants predict the development of asthma. Pediatr Allergy Immunol. 2004;15:159–162.
   PubMed Web of Science ®Google Scholar
• Naylor B. The shedding of the mucosa of the bronchial tree in asthma. Thorax. 1962;17:69–72.
   PubMedGoogle Scholar
• White SR. Apoptosis and the airway epithelium. J Allergy (Cairo). 2011;2011:948406.
   PubMedGoogle Scholar
• Zhou C, Yin G, Liu J, Liu X, Zhao S. Epithelial apoptosis and loss in airways of children with asthma. J Asthma. 2011;48:358–365.
   PubMed Web of Science ®Google Scholar
• Juncadella IJ, Kadl A, Sharma AK, et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature. 2013;493:547–551.
   PubMed Web of Science ®Google Scholar
• Barbato A, Turato G, Baraldo S, et al. Epithelial damage and angiogenesis in the airways of children with asthma. Am J Respir Crit Care Med. 2006;174:975–981.
   PubMed Web of Science ®Google Scholar
• Wang J, Sun H, Liu Y. The proliferative and anti-apoptosis functions of KGF/KGFR contributes to bronchial epithelial repair in asthma. Pulm Pharmacol Ther. 2020;63:101931.
   PubMed Web of Science ®Google Scholar
• Wan J, Cao Y, Abdelaziz MH, et al. Downregulated Rac1 promotes apoptosis and inhibits the clearance of apoptotic cells in airway epithelial cells, which may be associated with airway hyper-responsiveness in asthma. Scand J Immunol. 2019;89:e12752.
   PubMed Web of Science ®Google Scholar
• Yuan X, Wang E, Xiao X, et al. The role of IL-25 in the reduction of oxidative stress and the apoptosis of airway epithelial cells with specific immunotherapy in an asthma mouse model. Am J Transl Res. 2017;9:4137–4148.
   PubMed Web of Science ®Google Scholar
• James BN, Oyeniran C, Sturgill JL, et al. Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma. J Allergy Clin Immunol. 2021;147:1936–1948.e1939.
   PubMed Web of Science ®Google Scholar
• He X, Zhang L, Hu L, et al. PM2.5 Aggravated OVA-Induced Epithelial Tight Junction Disruption Through Fas Associated via Death Domain-Dependent Apoptosis in Asthmatic Mice. J Asthma Allergy. 2021;14:1411–1423.
   PubMed Web of Science ®Google Scholar
• Zhao C, Wang Y, Su Z, et al. Respiratory exposure to PM2.5 soluble extract disrupts mucosal barrier function and promotes the development of experimental asthma. Sci Total Environ. 2020;730:139145.
   PubMed Web of Science ®Google Scholar
• Aglietti RA, Estevez A, Gupta A, et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc Natl Acad Sci U S A. 2016;113:7858–7863.
   PubMed Web of Science ®Google Scholar
• Duncan CJ, Lawrie A, Blaylock MG, Douglas JG, Walsh GM. Reduced eosinophil apoptosis in induced sputum correlates with asthma severity. Eur Respir J. 2003;22:484–490.
   PubMed Web of Science ®Google Scholar
• Jackson DJ, Korn S, Mathur SK, et al. Safety of eosinophil-depleting therapy for severe, eosinophilic asthma: focus on benralizumab. Drug Saf. 2020;43:409–425.
   PubMed Web of Science ®Google Scholar
• Kankaanranta H, Lindsay MA, Giembycz MA, Zhang X, Moilanen E, Barnes PJ. Delayed eosinophil apoptosis in asthma. J Allergy Clin Immunol. 2000;106:77–83.
   PubMed Web of Science ®Google Scholar
• Tai PC, Sun L, Spry CJ. Effects of IL-5, granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-3 on the survival of human blood eosinophils in vitro. Clin Exp Immunol. 1991;85:312–316.
   PubMed Web of Science ®Google Scholar
• Felton JM, Dorward DA, Cartwright JA, et al. Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation. Thorax. 2020;75:600–605.
   PubMed Web of Science ®Google Scholar
• Ilmarinen P, Kankaanranta H. Eosinophil apoptosis as a therapeutic target in allergic asthma. Basic Clin Pharmacol Toxicol. 2014;114:109–117.
   PubMed Web of Science ®Google Scholar
• Januskevicius A, Janulaityte I, Kalinauskaite-Zukauske V, Gosens R, Malakauskas K. The enhanced adhesion of eosinophils is associated with their prolonged viability and pro-proliferative effect in asthma. J Clin Med. 2019;8:127.
   PubMed Web of Science ®Google Scholar
• Druilhe A, Létuvé S, Pretolani M. Glucocorticoid-induced apoptosis in human eosinophils: mechanisms of action. Apoptosis. 2003;8:481–495.
   PubMed Web of Science ®Google Scholar
• Zhu M, Yang J, Chen Y. Efficacy and safety of treatment with benralizumab for eosinophilic asthma. Int Immunopharmacol. 2022;111:109131.
   PubMed Web of Science ®Google Scholar
• Peters MC, Wenzel SE. Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma. Lancet. 2020;395:371–383.
   PubMed Web of Science ®Google Scholar
• Zhang J, Zhu Z, Zuo X, et al. The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma. Respir Res. 2020;21:170.
   PubMed Web of Science ®Google Scholar
• Tanaka A, Sato H, Akimoto K, Matsunaga T, Sagara H. Spontaneous sputum discriminates inflammatory phenotypes in patients with asthma. Ann Allergy Asthma Immunol. 2021;126:54–60.e51.
   PubMed Web of Science ®Google Scholar
• Chen F, Yu M, Zhong Y, Hua W, Huang H. The role of neutrophils in asthma. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021;50:123–130.
   PubMedGoogle Scholar
• Uddin M, Nong G, Ward J, et al. Prosurvival activity for airway neutrophils in severe asthma. Thorax. 2010;65:684–689.
   PubMed Web of Science ®Google Scholar
• Parfrey H, Farahi N, Porter L, Chilvers ER. Live and let die: is neutrophil apoptosis defective in severe asthma? Thorax. 2010;65:665–667.
   PubMed Web of Science ®Google Scholar
• Ciepiela O, Ostafin M, Demkow U. Neutrophils in asthma--a review. Respir Physiol Neurobiol. 2015;209:13–16.
   PubMed Web of Science ®Google Scholar
• Sharifi L, Karimi A, Shokouhi Shoormasti R, et al. Asthma Symptoms and Specific IgE Levels among Toluene Diisocyanate (TDI) Exposed Workers in Tehran, Iran. Iran J Public Health. 2013;42:397–401.
   PubMed Web of Science ®Google Scholar
• Choi Y, Sim S, Park HS. Is TLR4 critical for neutrophil apoptosis in occupational asthma? Allergy Asthma Immunol Res. 2020;12:560–562.
   PubMed Web of Science ®Google Scholar
• Chen S, Deng Y, He Q, et al. Toll-like Receptor 4 Deficiency Aggravates Airway Hyperresponsiveness and Inflammation by Impairing Neutrophil Apoptosis in a Toluene Diisocyanate-Induced Murine Asthma Model. Allergy Asthma Immunol Res. 2020;12:608–625.
   PubMed Web of Science ®Google Scholar
• Kim DH, Gu A, Lee JS, et al. Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma. Int J Med Sci. 2020;17:498–509.
   PubMed Web of Science ®Google Scholar
• Olave C, Alvarez P, Uberti B, et al. Tamoxifen induces apoptosis and inhibits respiratory burst in equine neutrophils independently of estrogen receptors. J Vet Pharmacol Ther. 2019;42:248–254.
   PubMed Web of Science ®Google Scholar
• Tsai YG, Chien JW, Chen WL, Shieh JJ, Lin CY. Induced apoptosis of TH2 lymphocytes in asthmatic children treated with Dermatophagoides pteronyssinus immunotherapy. Pediatr Allergy Immunol. 2005;16:602–608.
   PubMed Web of Science ®Google Scholar
• Hamzaoui A, Hamzaoui K, Salah H, Chabbou A. Lymphocytes apoptosis in patients with acute exacerbation of asthma. Mediators Inflamm. 1999;8:237–243.
   PubMed Web of Science ®Google Scholar
• Lamb JP, James A, Carroll N, Siena L, Elliot J, Vignola AM. Reduced apoptosis of memory T-cells in the inner airway wall of mild and severe asthma. Eur Respir J. 2005;26:265–270.
   PubMed Web of Science ®Google Scholar
• Mo Y, Ye L, Cai H, et al. SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells. Respir Res. 2021;22:178.
   PubMed Web of Science ®Google Scholar
• Dorscheid DR, Wojcik KR, Sun S, Marroquin B, White SR. Apoptosis of airway epithelial cells induced by corticosteroids. Am J Respir Crit Care Med. 2001;164:1939–1947.
   PubMed Web of Science ®Google Scholar
• Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. 2020;17:395–417.
   PubMed Web of Science ®Google Scholar
• Tian BP, Xia LX, Bao ZQ, et al. Bcl-2 inhibitors reduce steroid-insensitive airway inflammation. J Allergy Clin Immunol. 2017;140:418–430.
   PubMed Web of Science ®Google Scholar
• Tian BP, Li F, Li R, et al. Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis. Biomaterials. 2019;192:429–439.
   PubMed Web of Science ®Google Scholar
• Ma JX, Xiao X, Zhou KF, et al. Herb pair of Ephedrae Herba-Armeniacae Semen Amarum alleviates airway injury in asthmatic rats. J Ethnopharmacol. 2021;269:113745.
   PubMed Web of Science ®Google Scholar
• Tang J, Liu J, Zhang X. The Role of Osthole on TGF-β-Induced Lung Epithelium Apoptosis Injury and Epithelial-Mesenchymal Transition-Mediated Airway Remodeling in Pediatric Asthma. J Healthc Eng. 2022;2022:7099097.
   PubMed Web of Science ®Google Scholar
• Yu H, Huang X, Zhu HH, et al. Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway. Phytomedicine. 2023;111:154646.
   PubMed Web of Science ®Google Scholar
• Ma Z, Tang X, Gao Y, Wang H, Yu P, Liu R. Combined Extracts of Epimedii Folium and Ligustri Lucidi Fructus with Budesonide Attenuate Airway Remodeling in the Asthmatic Rats by Regulating Apoptosis and Autophagy. Evid Based Complement Alternat Med. 2020;2020:2319409.
   PubMed Web of Science ®Google Scholar
• Kobayashi S. Choose Delicately and Reuse Adequately: the Newly Revealed Process of Autophagy. Biol Pharm Bull. 2015;38:1098–1103.
   PubMed Web of Science ®Google Scholar
• Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol. 2008;9:1004–1010.
   PubMed Web of Science ®Google Scholar
• Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer. 2020;19:12.
   PubMed Web of Science ®Google Scholar
• Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell. 2019;176:11–42.
   PubMed Web of Science ®Google Scholar
• Ornatowski W, Lu Q, Yegambaram M, et al. Complex interplay between autophagy and oxidative stress in the development of pulmonary disease. Redox Biol. 2020;36:101679.
   PubMed Web of Science ®Google Scholar
• Hara T, Takamura A, Kishi C, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181:497–510.
   PubMed Web of Science ®Google Scholar
• Racanelli AC, Choi AMK, Choi ME. Autophagy in chronic lung disease. Prog Mol Biol Transl Sci. 2020;172:135–156.
   PubMed Web of Science ®Google Scholar
• Sachdeva K, Do DC, Zhang Y, Hu X, Chen J, Gao P. Environmental Exposures and Asthma Development: autophagy, Mitophagy, and Cellular Senescence. Front Immunol. 2019;10:2787.
   PubMed Web of Science ®Google Scholar
• Springer MZ, Macleod KF. In Brief: mitophagy: mechanisms and role in human disease. J Pathol. 2016;240:253–255.
   PubMed Web of Science ®Google Scholar
• Kerr JS, Adriaanse BA, Greig NH, et al. Mitophagy and alzheimer’s disease: cellular and molecular mechanisms. Trends Neurosci. 2017;40:151–166.
   PubMed Web of Science ®Google Scholar
• Li A, Gao M, Liu B, et al. Mitochondrial autophagy: molecular mechanisms and implications for cardiovascular disease. Cell Death Dis. 2022;13:444.
   PubMed Web of Science ®Google Scholar
• Catarino S, Pereira P, Girão H. Molecular control of chaperone-mediated autophagy. Essays Biochem. 2017;61:663–674.
   PubMed Web of Science ®Google Scholar
• Martin LJ, Gupta J, Jyothula SS, et al. Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. PLoS One. 2012;7:e33454.
   PubMed Web of Science ®Google Scholar
• Ahmad ES, Diab SM, Behiry EG, Bassyoni S, Ishak SR, Ramadan A. Autophagy-related 5 gene mRNA expression and ATG5 rs510432 polymorphism in children with bronchial asthma. Pediatr Pulmonol. 2022;57:2659.
   PubMed Web of Science ®Google Scholar
• Pham DL, Kim SH, Losol P, et al. Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma. Korean J Intern Med. 2016;31:375–385.
   PubMed Web of Science ®Google Scholar
• Poon AH, Choy DF, Chouiali F, et al. Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics. Front Immunol. 2017;8:355.
   PubMed Web of Science ®Google Scholar
• Yang F, Kong J, Zong Y, et al. Autophagy-related genes are involved in the progression and prognosis of asthma and regulate the immune microenvironment. Front Immunol. 2022;13:897835.
   PubMed Web of Science ®Google Scholar
• Poon AH, Chouiali F, Tse SM, et al. Genetic and histologic evidence for autophagy in asthma pathogenesis. J Allergy Clin Immunol. 2012;129:569–571.
   PubMed Web of Science ®Google Scholar
• Liu T, Liu Y, Miller M, et al. Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma. Am J Physiol Lung Cell Mol Physiol. 2017;313:L27–l40.
   PubMed Web of Science ®Google Scholar
• Li W, Wu Y, Zhao Y, et al. MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation. Thorax. 2020;75:1047–1057.
   PubMed Web of Science ®Google Scholar
• Dickinson JD, Alevy Y, Malvin NP, et al. IL13 activates autophagy to regulate secretion in airway epithelial cells. Autophagy. 2016;12:397–409.
   PubMed Web of Science ®Google Scholar
• Sweeter JM, Kudrna K, Hunt K, et al. Autophagy of mucin granules contributes to resolution of airway mucous metaplasia. Sci Rep. 2021;11:13037.
   PubMed Web of Science ®Google Scholar
• Winkler T, Frey U. Airway remodeling: shifting the trigger point for exacerbations in asthma. J Allergy Clin Immunol. 2021;148:710–712.
   PubMed Web of Science ®Google Scholar
• Bartis D, Mise N, Mahida RY, Eickelberg O, Thickett DR. Epithelial-mesenchymal transition in lung development and disease: does it exist and is it important? Thorax. 2014;69:760–765.
   PubMed Web of Science ®Google Scholar
• Jiao B, Chen Y, Yang Y, et al. Toluene diisocyanate-induced inflammation and airway remodeling involves autophagy in human bronchial epithelial cells. Toxicol In Vitro. 2021;70:105040.
   PubMed Web of Science ®Google Scholar
• Joseph C, Tatler AL. Pathobiology of airway remodeling in asthma: the emerging role of integrins. J Asthma Allergy. 2022;15:595–610.
   PubMed Web of Science ®Google Scholar
• McAlinden KD, Deshpande DA, Ghavami S, et al. Autophagy activation in asthma airways remodeling. Am J Respir Cell Mol Biol. 2019;60:541–553.
   PubMed Web of Science ®Google Scholar
• Ramakrishnan RK, Bajbouj K, Hachim MY, et al. Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients. PLoS One. 2020;15:e0242695.
   PubMed Web of Science ®Google Scholar
• Ramakrishnan RK, Bajbouj K, Al Heialy S, et al. IL-17 Induced Autophagy Regulates Mitochondrial Dysfunction and Fibrosis in Severe Asthmatic Bronchial Fibroblasts. Front Immunol. 2020;11:1002.
   PubMed Web of Science ®Google Scholar
• Hurrell BP, Shafiei Jahani P, Akbari O. Social Networking of Group Two Innate Lymphoid Cells in Allergy and Asthma. Front Immunol. 2018;9:2694.
   PubMed Web of Science ®Google Scholar
• Galle-Treger L, Hurrell BP, Lewis G, et al. Autophagy is critical for group 2 innate lymphoid cell metabolic homeostasis and effector function. J Allergy Clin Immunol. 2020;145:502–517.e505.
   PubMed Web of Science ®Google Scholar
• Matsushita K, Yoshimoto T. B cell-intrinsic MyD88 signaling is essential for IgE responses in lungs exposed to pollen allergens. J Immunol. 2014;193:5791–5800.
   PubMed Web of Science ®Google Scholar
• Xia F, Deng C, Jiang Y, et al. IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma. Autophagy. 2018;14:450–464.
   PubMed Web of Science ®Google Scholar
• Ban GY, Pham DL, Trinh TH, et al. Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target. Clin Exp Allergy. 2016;46:48–59.
   PubMed Web of Science ®Google Scholar
• Pham DL, Ban GY, Kim SH, et al. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clin Exp Allergy. 2017;47:57–70.
   PubMed Web of Science ®Google Scholar
• Liu JN, Suh DH, Trinh HK, Chwae YJ, Park HS, Shin YS. The role of autophagy in allergic inflammation: a new target for severe asthma. Exp Mol Med. 2016;48:e243.
   PubMed Web of Science ®Google Scholar
• Silveira JS, Antunes GL, Kaiber DB, et al. Autophagy induces eosinophil extracellular traps formation and allergic airway inflammation in a murine asthma model. J Cell Physiol. 2020;235:267–280.
   PubMed Web of Science ®Google Scholar
• Barnes PJ, Baker J, Donnelly LE. Autophagy in asthma and chronic obstructive pulmonary disease. Clin Sci (Lond). 2022;136:733–746.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Maazi H, Sankaranarayanan I, et al. Lack of autophagy induces steroid-resistant airway inflammation. J Allergy Clin Immunol. 2016;137:1382–1389.e.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Aono Y, Akiyama N, et al. Involvement of autophagy in exacerbation of eosinophilic airway inflammation in a murine model of obese asthma. Autophagy. 2022;18:2216–2228.
   PubMed Web of Science ®Google Scholar
• Daubeuf F, Schall N, Petit-Demoulière N, Frossard N, Muller S. An autophagy modulator peptide prevents lung function decrease and corrects established inflammation in murine models of airway allergy. Cells. 2021;10:2659.
   PubMed Web of Science ®Google Scholar
• Liu M, Zhang Y, Dong L, Guo Z. Apelin-13 facilitates mitochondria homeostasis via mitophagy to prevent against airway oxidative injury in asthma. Mol Immunol. 2023;153:1–9.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Do DC, Hu X, et al. CaMKII oxidation regulates cockroach allergen-induced mitophagy in asthma. J Allergy Clin Immunol. 2021;147:1464–1477.e1411.
   PubMed Web of Science ®Google Scholar
• Yu Y, Men S, Zhang Y. miR-20a-5p ameliorates ovalbumin (OVA)-induced mouse model of allergic asthma through targeting ATG7-regulated cell death, fibrosis and inflammation. Int Immunopharmacol. 2021;95:107342.
   PubMed Web of Science ®Google Scholar
• Chicote J, Yuste VJ, Boix J, Ribas J. Cell Death Triggered by the Autophagy Inhibitory Drug 3-Methyladenine in Growing Conditions Proceeds With DNA Damage. Front Pharmacol. 2020;11:580343.
   PubMed Web of Science ®Google Scholar
• Redmann M, Benavides GA, Berryhill TF, et al. Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons. Redox Biol. 2017;11:73–81.
   PubMed Web of Science ®Google Scholar
• McAlinden KD, Kota A, Haghi M, Ghavami S, Sharma P. Pharmacologic Inhibition of Vacuolar H(+)ATPase Attenuates Features of Severe Asthma in Mice. Am J Respir Cell Mol Biol. 2020;62:117–120.
   PubMed Web of Science ®Google Scholar
• Mauthe M, Orhon I, Rocchi C, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14:1435–1455.
   PubMed Web of Science ®Google Scholar
• Amaravadi RK, Kimmelman AC, Debnath J. Targeting autophagy in cancer: recent advances and future directions. Cancer Discov. 2019;9:1167–1181.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Bravo-San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16:487–511.
   PubMed Web of Science ®Google Scholar
• Theofani E, Xanthou G. Autophagy: a Friend or Foe in Allergic Asthma? Int J Mol Sci. 2021;22.
   PubMed Web of Science ®Google Scholar
• Craparo EF, Drago SE, Quaglia F, Ungaro F, Cavallaro G. Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation. Drug Deliv Transl Res. 2022;12:1859–1872.
   PubMed Web of Science ®Google Scholar
• Fredriksson K, Fielhaber JA, Lam JK, et al. Paradoxical effects of rapamycin on experimental house dust mite-induced asthma. PLoS One. 2012;7:e33984.
   PubMed Web of Science ®Google Scholar
• Hua W, Liu H, Xia LX, et al. Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice. Respirology. 2015;20:1055–1065.
   PubMed Web of Science ®Google Scholar
• Boberg E, Weidner J, Malmhäll C, Calvén J, Corciulo C, Rådinger M. Rapamycin Dampens Inflammatory Properties of Bone Marrow ILC2s in IL-33-Induced Eosinophilic Airway Inflammation. Front Immunol. 2022;13:915906.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Jing Y, Qiao J, et al. Activation of the mTOR signaling pathway is required for asthma onset. Sci Rep. 2017;7:4532.
   PubMed Web of Science ®Google Scholar
• Gu W, Cui R, Ding T, et al. Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma. Respirology. 2017;22:533–541.
   PubMed Web of Science ®Google Scholar
• Maneechotesuwan K, Kasetsinsombat K, Wongkajornsilp A, Barnes PJ. Role of autophagy in regulating interleukin-10 and the responses to corticosteroids and statins in asthma. Clin Exp Allergy. 2021;51:1553–1565.
   PubMed Web of Science ®Google Scholar
• Gong S, Ji X, Su J, et al. Yeast Fermentate Prebiotic Ameliorates Allergic Asthma, Associating with Inhibiting Inflammation and Reducing Oxidative Stress Level through Suppressing Autophagy. Mediators Inflamm. 2021;2021:4080935.
   PubMed Web of Science ®Google Scholar
• Huang C, Peng M, Tong J, et al. Vitamin D ameliorates asthma-induced lung injury by regulating HIF-1α/Notch1 signaling during autophagy. Food Sci Nutr. 2022;10:2773–2785.
   PubMed Web of Science ®Google Scholar
• Song G, Zhang Y, Yu S, et al. Chrysophanol attenuates airway inflammation and remodeling through nuclear factor-kappa B signaling pathway in asthma. Phytother Res. 2019;33:2702–2713.
   PubMed Web of Science ®Google Scholar
• Wang S, Wuniqiemu T, Tang W, et al. Luteolin inhibits autophagy in allergic asthma by activating PI3K/Akt/mTOR signaling and inhibiting Beclin-1-PI3KC3 complex. Int Immunopharmacol. 2021;94:107460.
   PubMed Web of Science ®Google Scholar
• Li H, Bi Q, Cui H, Lv C, Wang M. Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma. BMC Complement Med Ther. 2021;21:21.
   PubMedGoogle Scholar
• Tirpude NV, Sharma A, Kumari M, Bhardwaj N. Vitexin restores lung homeostasis by targeting vicious loop between inflammatory aggravation and autophagy mediated via multiple redox cascade and myeloid cells alteration in experimental allergic asthma. Phytomedicine. 2022;96:153902.
   PubMed Web of Science ®Google Scholar
• Zhu X, Cao Y, Su M, et al. Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy. Mol Med Rep. 2021;24:1.
   Web of Science ®Google Scholar
• Cho IH, Choi YJ, Gong JH, Shin D, Kang MK, Kang YH. Astragalin inhibits autophagy-associated airway epithelial fibrosis. Respir Res. 2015;16:51.
   PubMed Web of Science ®Google Scholar
• Han X, Hu S, Yang Q, Sang X, Tang D, Cao G. Paeoniflorin ameliorates airway inflammation and immune response in ovalbumin induced asthmatic mice: from oxidative stress to autophagy. Phytomedicine. 2022;96:153835.
   PubMed Web of Science ®Google Scholar
• Bai Q, Wang Z, Piao Y, et al. Sesamin alleviates asthma airway inflammation by regulating mitophagy and mitochondrial apoptosis. J Agric Food Chem. 2022;70:4921–4933.
   PubMed Web of Science ®Google Scholar
• Chen X, Luo Y, Wang M, et al. Wuhu Decoction Regulates Dendritic Cell Autophagy in the Treatment of Respiratory Syncytial Virus (RSV)-Induced Mouse Asthma by AMPK/ULK1 Signaling Pathway. Med Sci Monit. 2019;25:5389–5400.
   PubMed Web of Science ®Google Scholar
• Yu L, Wang J, Zou Y, Zeng H, Cheng W, Jing X. Qingfei oral liquid inhibited autophagy to alleviate inflammation via mTOR signaling pathway in RSV-infected asthmatic mice. Biomed Pharmacother. 2021;138:111449.
   PubMed Web of Science ®Google Scholar
• Wang X, Gao Y, Yang Q, Fang X, Li Z. Pingchuanning decoction attenuates airway inflammation by suppressing autophagy via phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in rat models of asthma. J Cell Biochem. 2019;120:3833–3844.
   PubMed Web of Science ®Google Scholar
• Zhao H, Dong F, Li Y, et al. Inhibiting ATG5 mediated autophagy to regulate endoplasmic reticulum stress and CD4(+) T lymphocyte differentiation: mechanisms of acupuncture’s effects on asthma. Biomed Pharmacother. 2021;142:112045.
   PubMed Web of Science ®Google Scholar
• Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9:113–114.
   PubMed Web of Science ®Google Scholar
• Yang J, Hu S, Bian Y, et al. Targeting cell death: pyroptosis, ferroptosis, apoptosis and necroptosis in osteoarthritis. Front Cell Dev Biol. 2021;9:789948.
   PubMed Web of Science ®Google Scholar
• Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16:407–420.
   PubMed Web of Science ®Google Scholar
• Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6:128.
   PubMed Web of Science ®Google Scholar
• Hsu SK, Li CY, Lin IL, et al. Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment. Theranostics. 2021;11:8813–8835.
   PubMed Web of Science ®Google Scholar
• Wang Y, Yin B, Li D, Wang G, Han X, Sun X. GSDME mediates caspase-3-dependent pyroptosis in gastric cancer. Biochem Biophys Res Commun. 2018;495:1418–1425.
   PubMed Web of Science ®Google Scholar
• Hou J, Zhao R, Xia W, et al. PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. Nat Cell Biol. 2020;22:1264–1275.
   PubMed Web of Science ®Google Scholar
• Zhou Z, He H, Wang K, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science. 2020;368:eaaz7548.
   PubMed Web of Science ®Google Scholar
• Liu Y, Fang Y, Chen X, et al. Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol. 2020;5:435.
   Web of Science ®Google Scholar
• Queiroz GA, da Silva RR, Pires AO, et al. New variants in NLRP3 inflammasome genes increase risk for asthma and Blomia tropicalis-induced allergy in a Brazilian population. Cytokine X. 2020;2:100032.
   PubMedGoogle Scholar
• Kim SR, Kim DI, Kim SH, et al. NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation. Cell Death Dis. 2014;5:e1498.
   PubMed Web of Science ®Google Scholar
• Sebag SC, Koval OM, Paschke JD, et al. Mitochondrial CaMKII inhibition in airway epithelium protects against allergic asthma. JCI Insight. 2017;2:e88297.
   PubMed Web of Science ®Google Scholar
• Yang F, Wang T, Yan P, et al. Identification of pyroptosis-related subtypes and establishment of prognostic model and immune characteristics in asthma. Front Immunol. 2022;13:937832.
   PubMed Web of Science ®Google Scholar
• Ritter M, Straubinger K, Schmidt S, et al. Functional relevance of NLRP3 inflammasome-mediated interleukin (IL)-1β during acute allergic airway inflammation. Clin Exp Immunol. 2014;178:212–223.
   PubMed Web of Science ®Google Scholar
• Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature. 2008;453:1122–1126.
   PubMed Web of Science ®Google Scholar
• Ma M, Li G, Qi M, Jiang W, Zhou R. Inhibition of the Inflammasome Activity of NLRP3 Attenuates HDM-Induced Allergic Asthma. Front Immunol. 2021;12:718779.
   PubMed Web of Science ®Google Scholar
• Tsai YM, Chiang KH, Hung JY, et al. Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3 inflammasome. Int J Mol Med. 2018;41:757–764.
   PubMed Web of Science ®Google Scholar
• Zhuang J, Cui H, Zhuang L, et al. Bronchial epithelial pyroptosis promotes airway inflammation in a murine model of toluene diisocyanate-induced asthma. Biomed Pharmacother. 2020;125:109925.
   PubMed Web of Science ®Google Scholar
• Panganiban RA, Sun M, Dahlin A, et al. A functional splice variant associated with decreased asthma risk abolishes the ability of gasdermin B to induce epithelial cell pyroptosis. J Allergy Clin Immunol. 2018;142:1469–1478.e1462.
   PubMed Web of Science ®Google Scholar
• Li X, Christenson SA, Modena B, et al. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. J Allergy Clin Immunol. 2021;147:894–909.
   PubMed Web of Science ®Google Scholar
• Das S, Miller M, Beppu AK, et al. GSDMB induces an asthma phenotype characterized by increased airway responsiveness and remodeling without lung inflammation. Proc Natl Acad Sci U S A. 2016;113:13132–13137.
   PubMed Web of Science ®Google Scholar
• Rossios C, Pavlidis S, Hoda U, et al. Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma. J Allergy Clin Immunol. 2018;141:560–570.
   PubMed Web of Science ®Google Scholar
• Simpson JL, Phipps S, Baines KJ, Oreo KM, Gunawardhana L, Gibson PG. Elevated expression of the NLRP3 inflammasome in neutrophilic asthma. Eur Respir J. 2014;43:1067–1076.
   PubMed Web of Science ®Google Scholar
• Kim RY, Pinkerton JW, Essilfie AT, et al. Role for NLRP3 Inflammasome-mediated, IL-1β-Dependent Responses in Severe, Steroid-Resistant Asthma. Am J Respir Crit Care Med. 2017;196:283–297.
   PubMed Web of Science ®Google Scholar
• Awad F, Assrawi E, Jumeau C, et al. Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation. PLoS One. 2017;12:e0175336.
   PubMed Web of Science ®Google Scholar
• Lachowicz-Scroggins ME, Dunican EM, Charbit AR, et al. Extracellular DNA, neutrophil extracellular traps, and inflammasome activation in severe asthma. Am J Respir Crit Care Med. 2019;199:1076–1085.
   PubMed Web of Science ®Google Scholar
• Chen L, Hou W, Liu F, et al. Blockade of NLRP3/Caspase-1/IL-1β Regulated Th17/Treg Immune Imbalance and Attenuated the Neutrophilic Airway Inflammation in an Ovalbumin-Induced Murine Model of Asthma. J Immunol Res. 2022;2022:9444227.
   PubMed Web of Science ®Google Scholar
• Tan HT, Hagner S, Ruchti F, et al. Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice. Allergy. 2019;74:294–307.
   PubMed Web of Science ®Google Scholar
• Miethe S, Karsonova A, Karaulov A, Renz H. Obesity and asthma. J Allergy Clin Immunol. 2020;146:685–693.
   PubMed Web of Science ®Google Scholar
• Wood LG, Li Q, Scott HA, et al. Saturated fatty acids, obesity, and the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in asthmatic patients. J Allergy Clin Immunol. 2019;143:305–315.
   PubMed Web of Science ®Google Scholar
• Pinkerton JW, Kim RY, Brown AC, et al. Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma. J Allergy Clin Immunol. 2022;149:1270–1280.
   PubMed Web of Science ®Google Scholar
• Kim HY, Lee HJ, Chang YJ, et al. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med. 2014;20:54–61.
   PubMed Web of Science ®Google Scholar
• Hur J, Kang JY, Kim YK, Lee SY, Lee HY. Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model. Pulm Pharmacol Ther. 2021;67:102003.
   PubMed Web of Science ®Google Scholar
• Triantafilou K, Kar S, van Kuppeveld FJ, Triantafilou M. Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. Am J Respir Cell Mol Biol. 2013;49:923–934.
   PubMed Web of Science ®Google Scholar
• Bauer RN, Brighton LE, Mueller L, et al. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis. J Allergy Clin Immunol. 2012;130:958–967.e914.
   PubMed Web of Science ®Google Scholar
• Gordon EM, Yao X, Xu H, et al. Apolipoprotein E is a concentration-dependent pulmonary danger signal that activates the NLRP3 inflammasome and IL-1β secretion by bronchoalveolar fluid macrophages from asthmatic subjects. J Allergy Clin Immunol. 2019;144:426–441.e423.
   PubMed Web of Science ®Google Scholar
• Han M, Bentley JK, Rajput C, et al. Inflammasome activation is required for human rhinovirus-induced airway inflammation in naive and allergen-sensitized mice. Mucosal Immunol. 2019;12:958–968.
   PubMed Web of Science ®Google Scholar
• Jeong JS, Choi JY, Kim JS, et al. SARS-CoV-2 infection in severe asthma is associated with worsening of COVID-19 through respiratory NLRP3 inflammasome activation. Allergy. 2022.
   Web of Science ®Google Scholar
• Kashima S, Yorifuji T, Suzuki E. Asian dust and daily emergency ambulance calls among elderly people in Japan: an analysis of its double role as a direct cause and as an effect modifier. J Occup Environ Med. 2014;56:1277–1283.
   PubMed Web of Science ®Google Scholar
• Ko JW, Shin NR, Je-Oh L, et al. Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation. Regul Toxicol Pharmacol. 2020;112:104618.
   PubMed Web of Science ®Google Scholar
• Hitomi Y, Ebisawa M, Tomikawa M, et al. Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma. J Allergy Clin Immunol. 2009;124:779–785.e776.
   PubMed Web of Science ®Google Scholar
• Zasłona Z, Flis E, Wilk MM, et al. Caspase-11 promotes allergic airway inflammation. Nat Commun. 2020;11:1055.
   PubMed Web of Science ®Google Scholar
• Allen IC, Jania CM, Wilson JE, et al. Analysis of NLRP3 in the development of allergic airway disease in mice. J Immunol. 2012;188:2884–2893.
   PubMed Web of Science ®Google Scholar
• Huang C, Wang J, Zheng X, et al. Commensal bacteria aggravate allergic asthma via NLRP3/IL-1β signaling in post-weaning mice. J Autoimmun. 2018;93:104–113.
   PubMed Web of Science ®Google Scholar
• Madouri F, Guillou N, Fauconnier L, et al. Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation. J Mol Cell Biol. 2015;7:351–365.
   PubMed Web of Science ®Google Scholar
• Williams EJ, Negewo NA, Baines KJ. Role of the NLRP3 inflammasome in asthma: relationship with neutrophilic inflammation, obesity, and therapeutic options. J Allergy Clin Immunol. 2021;147:2060–2062.
   PubMed Web of Science ®Google Scholar
• Bakhshi S, Shamsi S. MCC950 in the treatment of NLRP3-mediated inflammatory diseases: latest evidence and therapeutic outcomes. Int Immunopharmacol. 2022;106:108595.
   PubMed Web of Science ®Google Scholar
• Wang L, Zha B, Shen Q, et al. Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation. J Immunol Res. 2018;2018:9021037.
   PubMed Web of Science ®Google Scholar
• Primiano MJ, Lefker BA, Bowman MR, et al. Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation. J Immunol. 2016;197:2421–2433.
   PubMed Web of Science ®Google Scholar
• Chen S, Yao L, Huang P, et al. Blockade of the NLRP3/caspase-1 axis ameliorates airway neutrophilic inflammation in a toluene diisocyanate-induced murine asthma model. Toxicol Sci. 2019;170:462–475.
   PubMed Web of Science ®Google Scholar
• Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov. 2018;17:588–606.
   PubMed Web of Science ®Google Scholar
• Lunding LP, Skouras DB, Vock C, Dinarello CA, Wegmann M. The NLRP3 inflammasome inhibitor, OLT1177(®), ameliorates experimental allergic asthma in mice. Allergy. 2022;77:1035–1038.
   PubMed Web of Science ®Google Scholar
• Klück V, Jansen T, Janssen M, et al. Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial. Lancet Rheumatol. 2020;2:e270–e280.
   PubMedGoogle Scholar
• Chen Y, He H, Lin B, et al. RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor. Cell Mol Immunol. 2021;18:1425–1436.
   PubMed Web of Science ®Google Scholar
• Corcoran SE, Halai R, Cooper MA. Pharmacological Inhibition of the Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome with MCC950. Pharmacol Rev. 2021;73:968–1000.
   PubMed Web of Science ®Google Scholar
• Wen S, Deng F, Li L, Xu L, Li X, Fan Q. VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation. J Diabetes Investig. 2022;13:22–33.
   PubMed Web of Science ®Google Scholar
• Coll RC, Schroder K, Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci. 2022;43:653–668.
   PubMed Web of Science ®Google Scholar
• Pascoe S, Kanniess F, Bonner J, Lloyd P, Lowe P, Beier J. A monoclonal antibody to IL-1β attenuates the late asthmatic response to antigen challenge in patients with mild asthma. Annu Congr Eur Resp Soc. 2006;752.
   Google Scholar
• Theofani E, Semitekolou M, Morianos I, Samitas K, Xanthou G. Targeting NLRP3 inflammasome activation in severe asthma. J Clin Med. 2019;8:1615.
   PubMed Web of Science ®Google Scholar
• Wang J, Li F, Ding J, et al. Investigation of the anti‑asthmatic activity of Oridonin on a mouse model of asthma. Mol Med Rep. 2016;14:2000–2006.
   PubMed Web of Science ®Google Scholar
• Arıkan-Ayyıldız Z, Karaman M, Özbal S, et al. Efficacy of parthenolide on lung histopathology in a murine model of asthma. Allergol Immunopathol. 2017;45:63–68.
   PubMed Web of Science ®Google Scholar
• Jaiswal A, Dash D, Singh R. Intranasal curcumin and dexamethasone combination ameliorates inflammasome (NLRP3) activation in lipopolysaccharide exposed asthma exacerbations. Toxicol Appl Pharmacol. 2022;436:115861.
   PubMed Web of Science ®Google Scholar
• Chen X, Xiao Z, Jiang Z, Jiang Y, Li W, Wang M. Schisandrin B Attenuates Airway Inflammation and Airway Remodeling in Asthma by Inhibiting NLRP3 Inflammasome Activation and Reducing Pyroptosis. Inflammation. 2021;44:2217–2231.
   PubMed Web of Science ®Google Scholar
• Zhao CC, Xu J, Xie QM, Zhang HY, Fei GH, Wu HM. Abscisic acid suppresses the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation. Phytother Res. 2021;35:3298–3309.
   PubMed Web of Science ®Google Scholar
• Pan L, Chen Y, Jiang Y, Sun Y, Han Y, Wang Y. Yanghe Pingchuan Granules Alleviate Airway Inflammation in Bronchial Asthma and Inhibit Pyroptosis by Blocking the TLR4/NF-κB/NRLP3 Signaling Pathway. Mediators Inflamm. 2022;2022:6561048.
   PubMed Web of Science ®Google Scholar
• Liu X, Shen J, Fan D, et al. Yupingfeng San Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice. Front Pharmacol. 2017;8:944.
   PubMed Web of Science ®Google Scholar
• Qin W, Wu X, Jia Y, et al. Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma. Biomed Pharmacother. 2019;118:109188.
   PubMed Web of Science ®Google Scholar
• Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–1072.
   PubMed Web of Science ®Google Scholar
• Andrews NC, Schmidt PJ. Iron homeostasis. Annu Rev Physiol. 2007;69:69–85.
   PubMed Web of Science ®Google Scholar
• Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 2015;59:298–308.
   PubMed Web of Science ®Google Scholar
• Xie Y, Hou W, Song X, et al. Ferroptosis: process and function. Cell Death Differ. 2016;23:369–379.
   PubMed Web of Science ®Google Scholar
• Shui S, Zhao Z, Wang H, Conrad M, Liu G. Non-enzymatic lipid peroxidation initiated by photodynamic therapy drives a distinct ferroptosis-like cell death pathway. Redox Biol. 2021;45:102056.
   PubMed Web of Science ®Google Scholar
• Zhang C, Liu N. Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer. Front Immunol. 2022;13:920059.
   PubMed Web of Science ®Google Scholar
• Lu S, Wang XZ, He C, et al. ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron. Acta Pharmacol Sin. 2021;42:1690–1702.
   PubMed Web of Science ®Google Scholar
• Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A. 2016;113:E4966–4975.
   PubMed Web of Science ®Google Scholar
• Xu W, Deng H, Hu S, et al. Role of Ferroptosis in Lung Diseases. J Inflamm Res. 2021;14:2079–2090.
   PubMed Web of Science ®Google Scholar
• Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156:317–331.
   PubMed Web of Science ®Google Scholar
• McBean GJ. The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino Acids. 2012;42:199–205.
   PubMed Web of Science ®Google Scholar
• Dixon SJ, Patel DN, Welsch M, et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 2014;3:e02523.
   PubMed Web of Science ®Google Scholar
• Ali MK, Kim RY, Brown AC, et al. Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma. Eur Respir J. 2020;55:5443.
   Web of Science ®Google Scholar
• Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature. 2014;509:105–109.
   PubMed Web of Science ®Google Scholar
• Zeng Z, Huang H, Zhang J, et al. HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma. FASEB j. 2022;36:e22359.
   PubMed Web of Science ®Google Scholar
• Wenzel SE, Tyurina YY, Zhao J, et al. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell. 2017;171:628–641.e626.
   PubMed Web of Science ®Google Scholar
• Nagasaki T, Schuyler AJ, Zhao J, et al. 15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation. J Clin Invest. 2022;132.
   Web of Science ®Google Scholar
• Han F, Li S, Yang Y, Bai Z. Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid peroxidation and disrupting iron homeostasis. Bioengineered. 2021;12:5279–5288.
   PubMed Web of Science ®Google Scholar
• Tang W, Dong M, Teng F, et al. Environmental allergens house dust mite-induced asthma is associated with ferroptosis in the lungs. Exp Ther Med. 2021;22:1483.
   PubMed Web of Science ®Google Scholar
• Yang N, Shang Y. Ferrostatin-1 and 3-Methyladenine Ameliorate Ferroptosis in OVA-Induced Asthma Model and in IL-13-Challenged BEAS-2B Cells. Oxid Med Cell Longev. 2022;2022:9657933.
   PubMed Web of Science ®Google Scholar
• Hajek AR, Lindley AR, Favoreto S, Carter R, Schleimer RP, Kuperman DA. 12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels. J Allergy Clin Immunol. 2008;122:633–639.e633.
   PubMed Web of Science ®Google Scholar
• Bao C, Liu C, Liu Q, et al. Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis. Int Immunopharmacol. 2022;109:108770.
   PubMed Web of Science ®Google Scholar
• Farr AC, Xiong MP. Challenges and Opportunities of Deferoxamine Delivery for Treatment of Alzheimer’s Disease, Parkinson’s Disease, and Intracerebral Hemorrhage. Mol Pharm. 2021;18:593–609.
   PubMedGoogle Scholar
• Miotto G, Rossetto M, Di Paolo ML, et al. Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol. 2020;28:101328.
   PubMed Web of Science ®Google Scholar
• Zilka O, Shah R, Li B, et al. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci. 2017;3:232–243.
   PubMed Web of Science ®Google Scholar
• Li Y, Yang Y, Yang Y. Multifaceted Roles of Ferroptosis in Lung Diseases. Front Mol Biosci. 2022;9:919187.
   PubMed Web of Science ®Google Scholar
• Wu Y, Chen H, Xuan N, et al. Induction of ferroptosis-like cell death of eosinophils exerts synergistic effects with glucocorticoids in allergic airway inflammation. Thorax. 2020;75:918–927.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wan R, Peng W, Zhao X, Bai W, Hu C. Quercetin alleviates ferroptosis accompanied by reducing M1 macrophage polarization during neutrophilic airway inflammation. Eur J Pharmacol. 2023;938:175407.
   PubMed Web of Science ®Google Scholar
• Tang W, Dong M, Teng F, et al. TMT-based quantitative proteomics reveals suppression of SLC3A2 and ATP1A3 expression contributes to the inhibitory role of acupuncture on airway inflammation in an OVA-induced mouse asthma model. Biomed Pharmacother. 2021;134:111001.
   PubMed Web of Science ®Google Scholar
• Tang W, Qin J, Zhou Y, et al. Regulation of ferroptosis and ACSL4-15LO1 pathway contributed to the anti-asthma effect of acupuncture. Int Immunopharmacol. 2023;115:109670.
   PubMed Web of Science ®Google Scholar
• Mathias LJ, Khong SM, Spyroglou L, et al. Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells. J Immunol. 2013;191:5914–5924.
   PubMed Web of Science ®Google Scholar
• Lim J, Heo J, Ju H, et al. Glutathione dynamics determine the therapeutic efficacy of mesenchymal stem cells for graft-versus-host disease via CREB1-NRF2 pathway. Sci Adv. 2020;6:eaba1334.
   PubMed Web of Science ®Google Scholar
• Kim RL, Bang JY, Kim J, et al. Mesenchymal stem cells exert their anti-asthmatic effects through macrophage modulation in a murine chronic asthma model. Sci Rep. 2022;12:9811.
   PubMed Web of Science ®Google Scholar
• Lv X, Dong M, Tang W, et al. Ferroptosis, novel therapeutics in asthma. Biomed Pharmacother. 2022;153:113516.
   PubMed Web of Science ®Google Scholar
• Degterev A, Huang Z, Boyce M, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005;1:112–119.
   PubMed Web of Science ®Google Scholar
• Pasparakis M, Vandenabeele P. Necroptosis and its role in inflammation. Nature. 2015;517:311–320.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Kepp O, Chan FK, Kroemer G. Necroptosis: mechanisms and Relevance to Disease. Annu Rev Pathol. 2017;12:103–130.
   PubMed Web of Science ®Google Scholar
• Kaiser WJ, Upton JW, Long AB, et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 2011;471:368–372.
   PubMed Web of Science ®Google Scholar
• Bertrand MJ, Milutinovic S, Dickson KM, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689–700.
   PubMed Web of Science ®Google Scholar
• Gao W, Wang X, Zhou Y, Wang X, Yu Y. Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduct Target Ther. 2022;7:196.
   PubMed Web of Science ®Google Scholar
• Ning J, Qiao L. The role of necroptosis in common respiratory diseases in children. Front Pediatr. 2022;10:945175.
   PubMed Web of Science ®Google Scholar
• Muniz-Junqueira MI, Barbosa-Marques SM, Junqueira LF. Morphological changes in eosinophils are reliable markers of the severity of an acute asthma exacerbation in children. Allergy. 2013;68:911–920.
   PubMed Web of Science ®Google Scholar
• Radonjic-Hoesli S, Wang X, de Graauw E, et al. Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) signaling pathway, which is counter-regulated by autophagy. J Allergy Clin Immunol. 2017;140:1632–1642.
   PubMed Web of Science ®Google Scholar
• He A, Chen J, Guan J, et al. Selective eosinophil necroptosis contributes to airway inflammation and remodeling in asthma. Allergy. 2022;77:3456–3459.
   PubMed Web of Science ®Google Scholar
• Han XA, Jie HY, Wang JH, et al. Necrostatin-1 Ameliorates Neutrophilic Inflammation in Asthma by Suppressing MLKL Phosphorylation to Inhibiting NETs Release. Front Immunol. 2020;11:666.
   PubMed Web of Science ®Google Scholar
• Hamzaoui A, Berraies A, Kaabachi W, Haifa M, Ammar J, Kamel H. Induced sputum levels of IL-33 and soluble ST2 in young asthmatic children. J Asthma. 2013;50:803–809.
   PubMed Web of Science ®Google Scholar
• Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–490.
   PubMed Web of Science ®Google Scholar
• Kurowska-Stolarska M, Stolarski B, Kewin P, et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol. 2009;183:6469–6477.
   PubMed Web of Science ®Google Scholar
• Shlomovitz I, Erlich Z, Speir M, et al. Necroptosis directly induces the release of full-length biologically active IL-33 in vitro and in an inflammatory disease model. Febs j. 2019;286:507–522.
   PubMed Web of Science ®Google Scholar
• Oikonomou N, Schuijs MJ, Chatzigiagkos A, et al. Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation. Mucosal Immunol. 2021;14:1160–1171.
   PubMed Web of Science ®Google Scholar
• Upton JW, Chan FK. Staying alive: cell death in antiviral immunity. Mol Cell. 2014;54:273–280.
   PubMed Web of Science ®Google Scholar
• Zhang T, Yin C, Boyd DF, et al. Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis. Cell. 2020;180:1115–1129.e1113.
   PubMed Web of Science ®Google Scholar
• Gaajetaan GR, Geelen TH, Vernooy JH, et al. Interferon-β induces a long-lasting antiviral state in human respiratory epithelial cells. J Infect. 2013;66:163–169.
   PubMed Web of Science ®Google Scholar
• Wark PA, Johnston SL, Bucchieri F, et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201:937–947.
   PubMed Web of Science ®Google Scholar
• Cerps SC, Menzel M, Mahmutovic Persson I, Bjermer L, Akbarshahi H, Uller L. Interferon-β deficiency at asthma exacerbation promotes MLKL mediated necroptosis. Sci Rep. 2018;8:4248.
   PubMed Web of Science ®Google Scholar
• Feldman AS, He Y, Moore ML, Hershenson MB, Hartert TV. Toward primary prevention of asthma. Reviewing the evidence for early-life respiratory viral infections as modifiable risk factors to prevent childhood asthma. Am J Respir Crit Care Med. 2015;191:34–44.
   PubMed Web of Science ®Google Scholar
• Simpson J, Loh Z, Ullah MA, et al. Respiratory Syncytial Virus Infection Promotes Necroptosis and HMGB1 Release by Airway Epithelial Cells. Am J Respir Crit Care Med. 2020;201:1358–1371.
   PubMed Web of Science ®Google Scholar
• Liu K, Hua S, Song L. PM2.5 exposure and asthma development: the key role of oxidative stress. Oxid Med Cell Longev. 2022;2022:3618806.
   PubMed Web of Science ®Google Scholar
• Luo J, Liu H, Hua S, Song L. The Correlation of PM2.5 Exposure with Acute Attack and Steroid Sensitivity in Asthma. Biomed Res Int. 2022;2022:2756147.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Zhang H, Yang X, Zhang Y, Feng S, Yan X. Fine particulate matter (PM(2.5)) enhances airway hyperresponsiveness (AHR) by inducing necroptosis in BALB/c mice. Environ Toxicol Pharmacol. 2019;68:155–163.
   PubMed Web of Science ®Google Scholar
• Niessen NM, Gibson PG, Baines KJ, et al. Sputum TNF markers are increased in neutrophilic and severe asthma and are reduced by azithromycin treatment. Allergy. 2021;76:2090–2101.
   PubMed Web of Science ®Google Scholar
• Zhang H, Ji J, Liu Q, Xu S. MUC1 downregulation promotes TNF-α-induced necroptosis in human bronchial epithelial cells via regulation of the RIPK1/RIPK3 pathway. J Cell Physiol. 2019;234:15080–15088.
   PubMed Web of Science ®Google Scholar
• Zhang H, Liu Q, Kong L, Xu S. Mucin 1 downregulation impairs the anti-necroptotic effects of glucocorticoids in human bronchial epithelial cells. Life Sci. 2019;221:168–177.
   PubMed Web of Science ®Google Scholar
• Degterev A, Hitomi J, Germscheid M, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008;4:313–321.
   PubMed Web of Science ®Google Scholar
• Takahashi N, Duprez L, Grootjans S, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012;3:e437.
   PubMed Web of Science ®Google Scholar
• Jeong JS, Lee KB, Kim SR, et al. Airway epithelial phosphoinositide 3-kinase-δ contributes to the modulation of fungi-induced innate immune response. Thorax. 2018;73:758–768.
   PubMed Web of Science ®Google Scholar