SIRT1 protects against urban particulate matter-induced airway inflammation

Abstract

Purpose

Particulate matter (PM) has been implicated as a risk factor for airway injury. However, the molecular mechanisms remain largely unclear. The goal of this study was to determine whether sirtuin1 (SIRT1), an anti-inflammatory and antiaging protein, protects against PM-induced airway inflammation.

Methods

The effect of SIRT1 on PM-induced airway inflammation was assessed by using in vivo models of airway inflammation induced by PM and in vitro culture of human bronchial epithelial (HBE) cells exposed to PM, resveratrol (SIRT1 activator), or both.

Results

PM-stimulated HBE cells showed a significant decrease in SIRT1 but a notable increase in inflammatory cytokines. SIRT1 gene silencing further enhanced PM-induced expression of inflammatory cytokines. In contrast, resveratrol, a SIRT1 activator, reduced the expression of these cytokines compared with the control cells. In vivo, SIRT1 expression was significantly decreased in lung tissues of PM-exposed mice. Interestingly, resveratrol treatment reversed the enhanced total cells, neutrophils and inflammatory cytokines in PM-induced mice. Moreover, SIRT1 mediated PM-induced inflammatory cytokines expression at least partly through MAPK pathways.

Conclusion

These findings suggest that SIRT1 is involved in the pathogenesis of PM-induced airway inflammation and activation of SIRT1 could prevent airway disorders or disease exacerbations induced by airborne particulate pollution.

Keywords:

• particulate matter
• SIRT1
• resveratrol
• airway inflammation

Supplementary materials

Figure S1 SIRT1 overexpression suppresses PM-induced inflammation response in HBE cells. Cells were transfected with Control or SIRT1 plasmid and were stimulated with PM. (A) SIRT1 expression was measured by Western blot. (B-F) The mRNA levels of SIRT1, IL-6, IL-8, IL-17A, and MUC5AC were assessed by RT-PCR.Data are representative of three independent experiments. Results are expressed as mean ± SD. *p<0.05, **p<0.01, and ****p<0.0001.

Abbreviations: SIRT1, Sirtuin 1; PM, Particulate matter; HBE, Human bronchial epithelial.

Figure S2 Resveratrol (Res) suppresses PM-induced airway inflammation. WT mice were exposed to PM for 3 days. Lungs and BALF were isolated 1 day after the last PM challenge. The inflammatory cytokines in the lung homogenate (A and B) and BALF (C and D) were assessed by using an enzyme-linked immunosorbent assay. Data are representative of three independent studies (n=5–6 mice per group per study). Results are expressed as mean ± SD. *p<0.05, **p<0.01, and ***p<0.001.

Abbreviations: PM, Particulate matter; WT, Wild type; BALF, Brochoalveolar lavage fluid; KC, Keratinocyte-derived Cytokine.

Acknowledgments

Financial support was provided by the National Natural Science Foundation of China (81670025), the Natural Science Foundation of Guangdong Province China (2018A0303130269), and the Doctoral Startup Found-ation of the Affiliated Hospital of Guangdong Medical University (Tianwen Lai).

Disclosure

The authors declare that they have no conflicts of interest regarding this manuscript.