Quercetin is a Potential Therapy for Rheumatoid Arthritis via Targeting Caspase-8 Through Ferroptosis and Pyroptosis

References

• Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631–637. doi:10.1136/ard.2009.123919
   PubMed Web of Science ®Google Scholar
• Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581. doi:10.1002/art.27584
   PubMed Web of Science ®Google Scholar
• McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328–2337. doi:10.1016/s0140-6736(17)31472-1
   PubMed Web of Science ®Google Scholar
• van der Woude D, van der Helm-van Mil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2018;32(2):174–187. doi:10.1016/j.berh.2018.10.005
   PubMed Web of Science ®Google Scholar
• Firestein GS, McInnes IB. Immunopathogenesis of Rheumatoid Arthritis. Immunity. 2017;46(2):183–196. doi:10.1016/j.immuni.2017.02.006
   PubMed Web of Science ®Google Scholar
• Farrugia M, Baron B. The role of TNF-α in rheumatoid arthritis: a focus on regulatory T cells. J Clin Trans Res. 2016;2(3):84–90.
   Google Scholar
• Zhao J, Jiang P, Guo S, et al. Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis. Front Immunol. 2021;12:809806. doi:10.3389/fimmu.2021.809806
   PubMed Web of Science ®Google Scholar
• Matsumura T, Saito Y, Suzuki T, et al. Phosphorylated Platelet-Derived Growth Factor Receptor-Positive Cells With Anti-apoptotic Properties Accumulate in the Synovium of Patients With Rheumatoid Arthritis. Front Immunol. 2019;10:241. doi:10.3389/fimmu.2019.00241
   PubMed Web of Science ®Google Scholar
• Zhu L, Wang H, Wu Y, et al. The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity. Mediators Inflamm. 2017;2017:7623145. doi:10.1155/2017/7623145
   PubMed Web of Science ®Google Scholar
• Zhou Y, Chen B, Mittereder N, et al. Spontaneous Secretion of the Citrullination Enzyme PAD2 and Cell Surface Exposure of PAD4 by Neutrophils. Front Immunol. 2017;8:1200. doi:10.3389/fimmu.2017.01200
   PubMed Web of Science ®Google Scholar
• Zhang DW, Shao J, Lin J, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009;325(5938):332–336. doi:10.1126/science.1172308
   PubMed Web of Science ®Google Scholar
• Zhao T, Yang Q, Xi Y, et al. Ferroptosis in Rheumatoid Arthritis: a Potential Therapeutic Strategy. Front Immunol. 2022;13:779585. doi:10.3389/fimmu.2022.779585
   PubMedGoogle Scholar
• Wu XY, Li KT, Yang HX, et al. Complement C1q synergizes with PTX3 in promoting NLRP3 inflammasome over-activation and pyroptosis in rheumatoid arthritis. J Autoimmun. 2020;106:102336. doi:10.1016/j.jaut.2019.102336
   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(5):1060–1072. doi:10.1016/j.cell.2012.03.042
   PubMed Web of Science ®Google Scholar
• Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017;171(2):273–285. doi:10.1016/j.cell.2017.09.021
   PubMed Web of Science ®Google Scholar
• Tański W, Chabowski M, Jankowska-Polańska B, et al. Iron metabolism in patients with rheumatoid arthritis. Eur Rev Med Pharmacol Sci. 2021;25(12):4325–4335. doi:10.26355/eurrev_202106_26140
   PubMed Web of Science ®Google Scholar
• Su LJ, Zhang JH, Gomez H, et al. Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis. Oxid Med Cell Longev. 2019;2019:5080843. doi:10.1155/2019/5080843
   PubMed Web of Science ®Google Scholar
• Quiñonez-Flores CM, González-Chávez SA, Del Río Nájera D, et al. Oxidative Stress Relevance in the Pathogenesis of the Rheumatoid Arthritis: a Systematic Review. Biomed Res Int. 2016;2016:6097417. doi:10.1155/2016/6097417
   PubMed Web of Science ®Google Scholar
• Mao H, Zhao Y, Li H, et al. Ferroptosis as an emerging target in inflammatory diseases. Prog Biophys Mol Biol. 2020;155:20–28. doi:10.1016/j.pbiomolbio.2020.04.001
   PubMed Web of Science ®Google Scholar
• Li P, Jiang M, Li K, et al. Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity. Nat Immunol. 2021;22(9):1107–1117. doi:10.1038/s41590-021-00993-3
   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(3):486–541. doi:10.1038/s41418-017-0012-4
   PubMed Web of Science ®Google Scholar
• Kovacs SB, Miao EA. Gasdermins: effectors of Pyroptosis. Trends Cell Biol. 2017;27(9):673–684. doi:10.1016/j.tcb.2017.05.005
   PubMed Web of Science ®Google Scholar
• Chadha S, Behl T, Bungau S, et al. Mechanistic insights into the role of pyroptosis in rheumatoid arthritis. Curr Res Transl Med. 2020;68(4):151–158. doi:10.1016/j.retram.2020.07.003
   PubMed Web of Science ®Google Scholar
• Chen KW, Demarco B, Heilig R, et al. Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly. EMBO j. 2019;38(10). doi:10.15252/embj.2019101638
   Web of Science ®Google Scholar
• Carullo G, Cappello AR, Frattaruolo L, et al. Quercetin and derivatives: useful tools in inflammation and pain management. Future Med Chem. 2017;9(1):79–93. doi:10.4155/fmc-2016-0186
   PubMed Web of Science ®Google Scholar
• Shen P, Lin W, Deng X, et al. Potential Implications of Quercetin in Autoimmune Diseases. Front Immunol. 2021;12:689044. doi:10.3389/fimmu.2021.689044
   PubMed Web of Science ®Google Scholar
• Xie R, Zhao W, Lowe S, et al. Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway. Free Radic Biol Med. 2022;191:212–226. doi:10.1016/j.freeradbiomed.2022.09.001
   PubMed Web of Science ®Google Scholar
• Wang Y, Quan F, Cao Q, et al. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res. 2021;28:231–243. doi:10.1016/j.jare.2020.07.007
   PubMed Web of Science ®Google Scholar
• Huang T, Zhang K, Wang J, et al. Quercetin Alleviates Acrylamide-Induced Liver Injury by Inhibiting Autophagy-Dependent Ferroptosis. J Agric Food Chem. 2023;71(19):7427–7439. doi:10.1021/acs.jafc.3c01378
   PubMed Web of Science ®Google Scholar
• Ye Y, Jiang M, Hong X, et al. Quercetin Alleviates Deoxynivalenol-Induced Intestinal Damage by Suppressing Inflammation and Ferroptosis in Mice. J Agric Food Chem. 2023. doi:10.1021/acs.jafc.3c02027
   Web of Science ®Google Scholar
• Luo X, Weng X, Bao X, et al. A novel anti-atherosclerotic mechanism of quercetin: competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis. Redox Biol. 2022;57:102511. doi:10.1016/j.redox.2022.102511
   PubMed Web of Science ®Google Scholar
• Wei Z, Jing Z, Pinfang K, et al. Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway. J Diabetes Res. 2022;2022:9723632. doi:10.1155/2022/9723632
   PubMed Web of Science ®Google Scholar
• Chen LL, Song C, Zhang Y, et al. Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation. Eur J Pharmacol. 2022;936:175352. doi:10.1016/j.ejphar.2022.175352
   PubMed Web of Science ®Google Scholar
• Chen HY, Chiang YF, Hong YH, et al. Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo. Antioxidants (Basel). 2022;11(11). doi:10.3390/antiox11112238
   Google Scholar
• Woetzel D, Huber R, Kupfer P, et al. Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation. Arthritis Res Ther. 2014;16(2):R84. doi:10.1186/ar4526
   PubMed Web of Science ®Google Scholar
• Broeren MG, de Vries M, Bennink MB, et al. Disease-Regulated Gene Therapy with Anti-Inflammatory Interleukin-10 Under the Control of the CXCL10 Promoter for the Treatment of Rheumatoid Arthritis. Hum Gene Ther. 2016;27(3):244–254. doi:10.1089/hum.2015.127
   PubMed Web of Science ®Google Scholar
• Zhou N, Bao J. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database. 2020;2020. doi:10.1093/database/baaa021
   Google Scholar
• Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database. 2010;2010:baq020. doi:10.1093/database/baq020
   PubMedGoogle Scholar
• Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. doi:10.1093/nar/gkv007
   PubMed Web of Science ®Google Scholar
• Wickham H. Ggplot2: elegant Graphics for Data Analysis: ggplot2: elegant Graphics for Data Analysis. Int J Med. 2009;1:567.
   Google Scholar
• Yu G, Wang LG, Han Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16(5):284–287. doi:10.1089/omi.2011.0118
   PubMed Web of Science ®Google Scholar
• Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607–d13. doi:10.1093/nar/gky1131
   PubMed Web of Science ®Google Scholar
• Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–2504. doi:10.1101/gr.1239303
   PubMed Web of Science ®Google Scholar
• Beck MW. NeuralNetTools: visualization and Analysis Tools for Neural Networks. J Stat Softw. 2018;85(11):1–20. doi:10.18637/jss.v085.i11
   PubMed Web of Science ®Google Scholar
• Zhou G, Soufan O, Ewald J, et al. NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019:47(W1):W234–w41. doi:10.1093/nar/gkz240
   Web of Science ®Google Scholar
• Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10(1):1523. doi:10.1038/s41467-019-09234-6
   PubMed Web of Science ®Google Scholar
• Warde-Farley D, Donaldson SL, Comes O, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38:W214–20. doi:10.1093/nar/gkq537
   PubMed Web of Science ®Google Scholar
• Rydenfelt M, Klinger B, Klünemann M, et al. SPEED2: inferring upstream pathway activity from differential gene expression. Nucleic Acids Res. 2020;48(W1):W307–w12. doi:10.1093/nar/gkaa236
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–408. doi:10.1006/meth.2001.1262
   PubMed Web of Science ®Google Scholar
• Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–457. doi:10.1038/nmeth.3337
   PubMed Web of Science ®Google Scholar
• Davis AP, Grondin CJ, Johnson RJ, et al. Comparative Toxicogenomics Database (CTD): update 2021. Nucleic Acids Res. 2021;49(D1):D1138–d43. doi:10.1093/nar/gkaa891
   PubMed Web of Science ®Google Scholar
• Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13. doi:10.1186/1758-2946-6-13
   PubMed Web of Science ®Google Scholar
• Nowotka MM, Gaulton A, Mendez D, et al. Using ChEMBL web services for building applications and data processing workflows relevant to drug discovery. Expert Opin Drug Discov. 2017;12(8):757–767. doi:10.1080/17460441.2017.1339032
   PubMed Web of Science ®Google Scholar
• Li Q, Cheng T, Wang Y, et al. PubChem as a public resource for drug discovery. Drug Discov Today. 2010;15(23–24):1052–1057. doi:10.1016/j.drudis.2010.10.003
   PubMed Web of Science ®Google Scholar
• Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235–242. doi:10.1093/nar/28.1.235
   PubMed Web of Science ®Google Scholar
• Luo H, Zhang R. Icariin enhances cell survival in lipopolysaccharide-induced synoviocytes by suppressing ferroptosis via the Xc-/GPX4 axis. Exp Ther Med. 2021;21(1):72. doi:10.3892/etm.2020.9504
   PubMed Web of Science ®Google Scholar
• Cen WJ, Feng Y, Li SS, et al. Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells. J Cell Physiol. 2018;233(9):6779–6789. doi:10.1002/jcp.26405
   PubMed Web of Science ®Google Scholar
• Xiao W, Beibei F, Guangsi S, et al. Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass. J Endocrinol. 2015;226(3):121–134. doi:10.1530/joe-14-0657
   PubMed Web of Science ®Google Scholar
• Hakobyan N, Kazarian T, Jabbar AA, et al. Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene. Blood. 2004;104(7):2060–2064. doi:10.1182/blood-2003-12-4231
   PubMed Web of Science ®Google Scholar
• Ogilvie-Harris DJ, Fornaiser VL. Synovial iron deposition in osteoarthritis and rheumatoid arthritis. J Rheumatol. 1980;7(1):30–36.
   PubMed Web of Science ®Google Scholar
• Datta S, Kundu S, Ghosh P, et al. Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis. Clin Rheumatol. 2014;33(11):1557–1564. doi:10.1007/s10067-014-2597-z
   PubMed Web of Science ®Google Scholar
• Xie Z, Hou H, Luo D, et al. ROS-Dependent Lipid Peroxidation and Reliant Antioxidant Ferroptosis-Suppressor-Protein 1 in Rheumatoid Arthritis: a Covert Clue for Potential Therapy. Inflammation. 2021;44(1):35–47. doi:10.1007/s10753-020-01338-2
   PubMed Web of Science ®Google Scholar
• Vande Walle L, Lamkanfi M. Pyroptosis. Curr Biol. 2016;26(13):R568–r72. doi:10.1016/j.cub.2016.02.019
   PubMed Web of Science ®Google Scholar
• He Y, Hara H, Núñez G. Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends Biochem Sci. 2016;41(12):1012–1021. doi:10.1016/j.tibs.2016.09.002
   PubMed Web of Science ®Google Scholar
• Franchi L, Muñoz-Planillo R, Núñez G. Sensing and reacting to microbes through the inflammasomes. Nat Immunol. 2012;13(4):325–332. doi:10.1038/ni.2231
   PubMed Web of Science ®Google Scholar
• Lang T, Lee JPW, Elgass K, et al. Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation. Nat Commun. 2018;9(1):2223. doi:10.1038/s41467-018-04581-2
   PubMedGoogle Scholar
• Bauernfeind FG, Horvath G, Stutz A, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 2009;183(2):787–791. doi:10.4049/jimmunol.0901363
   PubMed Web of Science ®Google Scholar
• Franchi L, Eigenbrod T, Muñoz-Planillo R, et al. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009;10(3):241–247. doi:10.1038/ni.1703
   PubMed Web of Science ®Google Scholar
• Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660–665. doi:10.1038/nature15514
   PubMed Web of Science ®Google Scholar
• Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535(7610):111–116. doi:10.1038/nature18590
   PubMed Web of Science ®Google Scholar
• Liu X, Zhang Z, Ruan J, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535(7610):153–158. doi:10.1038/nature18629
   PubMed Web of Science ®Google Scholar
• Boucher D, Monteleone M, Coll RC, et al. Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J Exp Med. 2018;215(3):827–840. doi:10.1084/jem.20172222
   PubMed Web of Science ®Google Scholar
• Lamkanfi M, Declercq W, Kalai M, et al. Alice in caspase land. A phylogenetic analysis of caspases from worm to man. Cell Death Differ. 2002;9(4):358–361. doi:10.1038/sj.cdd.4400989
   PubMed Web of Science ®Google Scholar
• Ramirez MLG, Salvesen GS. A primer on caspase mechanisms. Semin Cell Dev Biol. 2018;82:79–85. doi:10.1016/j.semcdb.2018.01.002
   PubMed Web of Science ®Google Scholar
• Van Opdenbosch N, Lamkanfi M. Caspases in Cell Death, Inflammation, and Disease. Immunity. 2019;50(6):1352–1364. doi:10.1016/j.immuni.2019.05.020
   PubMed Web of Science ®Google Scholar
• Shi J, Zhao Y, Wang Y, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 2014;514(7521):187–192. doi:10.1038/nature13683
   PubMed Web of Science ®Google Scholar
• Wang Y, Gao W, Shi X, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547(7661):99–103. doi:10.1038/nature22393
   PubMed Web of Science ®Google Scholar
• Antonopoulos C, Russo HM, El Sanadi C, et al. Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling. J Biol Chem. 2015;290(33):20167–20184. doi:10.1074/jbc.M115.652321
   PubMed Web of Science ®Google Scholar
• Tummers B, Green DR. Caspase-8: regulating life and death. Immunol Rev. 2017;277(1):76–89. doi:10.1111/imr.12541
   PubMed Web of Science ®Google Scholar
• Fritsch M, Günther SD, Schwarzer R, et al. Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature. 2019;575(7784):683–687. doi:10.1038/s41586-019-1770-6
   PubMed Web of Science ®Google Scholar
• Mandal R, Barrón JC, Kostova I, et al. Caspase-8: the double-edged sword. Biochim Biophys Acta Rev Cancer. 2020;1873(2):188357. doi:10.1016/j.bbcan.2020.188357
   PubMed Web of Science ®Google Scholar
• Newton K, Wickliffe KE, Maltzman A, et al. Activity of caspase-8 determines plasticity between cell death pathways. Nature. 2019;575(7784):679–682. doi:10.1038/s41586-019-1752-8
   PubMed Web of Science ®Google Scholar
• Gurung P, Kanneganti TD. Novel roles for caspase-8 in IL-1β and inflammasome regulation. Am J Pathol. 2015;185(1):17–25. doi:10.1016/j.ajpath.2014.08.025
   PubMed Web of Science ®Google Scholar
• Monie TP, Bryant CE. Caspase-8 functions as a key mediator of inflammation and pro-IL-1β processing via both canonical and non-canonical pathways. Immunol Rev. 2015;265(1):181–193. doi:10.1111/imr.12284
   PubMed Web of Science ®Google Scholar
• Han JH, Park J, Kang TB, et al. Regulation of Caspase-8 Activity at the Crossroads of Pro-Inflammation and Anti-Inflammation. Int J Mol Sci. 2021;22(7). doi:10.3390/ijms22073318
   Web of Science ®Google Scholar
• Ganesan S, Rathinam VAK, Bossaller L, et al. Caspase-8 modulates dectin-1 and complement receptor 3-driven IL-1β production in response to β-glucans and the fungal pathogen, Candida albicans. J Immunol. 2014;193(5):2519–2530. doi:10.4049/jimmunol.1400276
   PubMed Web of Science ®Google Scholar
• Lawlor KE, Khan N, Mildenhall A, et al. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun. 2015;6:6282. doi:10.1038/ncomms7282
   PubMed Web of Science ®Google Scholar
• Maelfait J, Vercammen E, Janssens S, et al. Stimulation of Toll-like receptor 3 and 4 induces interleukin-1beta maturation by caspase-8. J Exp Med. 2008;205(9):1967–1973. doi:10.1084/jem.20071632
   PubMed Web of Science ®Google Scholar
• Sagulenko V, Thygesen SJ, Sester DP, et al. AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death Differ. 2013;20(9):1149–1160. doi:10.1038/cdd.2013.37
   PubMed Web of Science ®Google Scholar
• Schwarzer R, Jiao H, Wachsmuth L, et al. FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells. Immunity. 2020;52(6):978–93.e6. doi:10.1016/j.immuni.2020.04.002
   PubMed Web of Science ®Google Scholar
• Gurung P, Anand PK, Malireddi RK, et al. FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J Immunol. 2014;192(4):1835–1846. doi:10.4049/jimmunol.1302839
   PubMed Web of Science ®Google Scholar
• Allam R, Lawlor KE, Yu EC, et al. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep. 2014;15(9):982–990. doi:10.15252/embr.201438463
   PubMed Web of Science ®Google Scholar
• Kim WS, Lee KS, Kim JH, et al. The caspase-8/Bid/cytochrome c axis links signals from death receptors to mitochondrial reactive oxygen species production. Free Radic Biol Med. 2017;112:567–577. doi:10.1016/j.freeradbiomed.2017.09.001
   PubMed Web of Science ®Google Scholar
• Yao X, Li W, Fang D, et al. Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells. Adv Sci. 2021;8(22):e2100997. doi:10.1002/advs.202100997
   Web of Science ®Google Scholar
• Lawlor KE, Feltham R, Yabal M, et al. XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation. Cell Rep. 2017;20(3):668–682. doi:10.1016/j.celrep.2017.06.073
   PubMed Web of Science ®Google Scholar
• Xia J, Zhang J, Wang L, et al. Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide resistance via NF-κB activation. Cell Death Dis. 2021;12(9):833. doi:10.1038/s41419-021-04126-4
   PubMed Web of Science ®Google Scholar
• Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–255. doi:10.1111/j.0105-2896.2009.00859.x
   PubMed Web of Science ®Google Scholar
• Masoumi M, Bashiri H, Khorramdelazad H, et al. Destructive Roles of Fibroblast-like Synoviocytes in Chronic Inflammation and Joint Damage in Rheumatoid Arthritis. Inflammation. 2021;44(2):466–479. doi:10.1007/s10753-020-01371-1
   PubMed Web of Science ®Google Scholar
• McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429–442. doi:10.1038/nri2094
   PubMed Web of Science ®Google Scholar
• Chi PL, Liu CJ, Lee IT, et al. HO-1 induction by CO-RM2 attenuates TNF-α-induced cytosolic phospholipase A2 expression via inhibition of PKCα-dependent NADPH oxidase/ROS and NF-κB. Mediators Inflamm. 2014;2014:279171. doi:10.1155/2014/279171
   PubMed Web of Science ®Google Scholar
• Roberge S, Roussel J, Andersson DC, et al. TNF-α-mediated caspase-8 activation induces ROS production and TRPM2 activation in adult ventricular myocytes. Cardiovasc Res. 2014;103(1):90–99. doi:10.1093/cvr/cvu112
   PubMed Web of Science ®Google Scholar
• Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21(1):103–115. doi:10.1038/cr.2010.178
   PubMed Web of Science ®Google Scholar
• Chemin K, Gerstner C, Malmström V. Effector Functions of CD4+ T Cells at the Site of Local Autoimmune Inflammation-Lessons From Rheumatoid Arthritis. Front Immunol. 2019;10:353. doi:10.3389/fimmu.2019.00353
   PubMed Web of Science ®Google Scholar
• Murakami M, Hirano T. A four-step model for the IL-6 amplifier, a regulator of chronic inflammations in tissue-specific MHC class II-associated autoimmune diseases. Front Immunol. 2011;2:22. doi:10.3389/fimmu.2011.00022
   PubMed Web of Science ®Google Scholar
• Carbone G, Wilson A, Diehl SA, et al. Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and IgG4 autoantibodies in rheumatoid arthritis. Int J Biol Sci. 2013;9(3):279–288. doi:10.7150/ijbs.5996
   PubMed Web of Science ®Google Scholar
• Zhou S, Lu H, Xiong M. Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis. Front Immunol. 2021;12:726747. doi:10.3389/fimmu.2021.726747
   PubMed Web of Science ®Google Scholar
• Cascão R, Moura RA, Perpétuo I, et al. Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis. Arthritis Res Ther. 2010;12(5):R196. doi:10.1186/ar3168
   PubMed Web of Science ®Google Scholar
• Martin BN, Wang C, Zhang CJ, et al. T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis. Nat Immunol. 2016;17(5):583–592. doi:10.1038/ni.3389
   PubMed Web of Science ®Google Scholar
• Javadi F, Ahmadzadeh A, Eghtesadi S, et al. The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: a Double-Blind, Randomized Controlled Trial. J Am Coll Nutr. 2017;36(1):9–15. doi:10.1080/07315724.2016.1140093
   PubMed Web of Science ®Google Scholar
• Yang Y, Zhang X, Xu M, et al. Quercetin attenuates collagen-induced arthritis by restoration of Th17/Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect. Int Immunopharmacol. 2018;54:153–162. doi:10.1016/j.intimp.2017.11.013
   PubMed Web of Science ®Google Scholar
• Kawaguchi K, Kaneko M, Miyake R, et al. Potent Inhibitory Effects of Quercetin on Inflammatory Responses of Collagen-Induced Arthritis in Mice. Endocr Metab Immune Disord Drug Targets. 2019;19(3):308–315. doi:10.2174/1871530319666190206225034
   PubMed Web of Science ®Google Scholar
• Kim HR, Kim BM, Won JY, et al. Quercetin, a Plant Polyphenol, Has Potential for the Prevention of Bone Destruction in Rheumatoid Arthritis. J Med Food. 2019;22(2):152–161. doi:10.1089/jmf.2018.4259
   PubMed Web of Science ®Google Scholar
• Saccol R, da Silveira KL, Manzoni AG, et al. Antioxidant, hepatoprotective, genoprotective, and cytoprotective effects of quercetin in a murine model of arthritis. J Cell Biochem. 2020;121(4):2792–2801. doi:10.1002/jcb.29502
   PubMed Web of Science ®Google Scholar