Interleukin-37 inhibits inflammation activation and disease severity of PM2.5-induced airway hyperresponsiveness

• Published in: Ecotoxicology and environmental safety Vol. 227; p. 112890
• Main Authors: Wang, Min, Hou, Shujie, Lu, Xi, Li, Jingwen, Li, Rongqin, Yan, Xixin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 20-12-2021; Elsevier
• Subjects: airway hyperresponsiveness; Animals; fine particulate matter (PM2.5); human airway smooth muscle cells, IL-1R8; Humans; Inflammation - chemically induced; interleukin (IL)-37; Interleukin-1; Lung; Mice; Particulate Matter - toxicity; Respiratory Hypersensitivity - chemically induced; Severity of Illness Index; airway hyperresponsiveness; IL; Mch; fine particulate matter (PM2.5); FBS; PM2.5; BALF; IL-37tg; hASMC; FA; interleukin (IL)-37; human airway smooth muscle cells, IL-1R8
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.112890

We have shown in the past studies that fine particulate matter (PM2.5) exposure increases airway hyperresponsiveness and leads to lung inflammation damage. Interleukin (IL)-37 plays a inhibitory role in inflammation activation and maintenance. However, the function of IL-37 in the above processes keep unclear. We aim to explore the role of IL-37 in PM2.5-induced airway hyperresponsiveness in this study. A nose-only PM2.5 online concentration, enrichment and exposure instrument was also applied to generate mice model of airway hyperresponsiveness. A transgenic mice strain using a CMV promoter to express human IL-37b (hIL-37tg) was obtained. PM2.5 exposure was shown to increase airway resistance, followed by lung inflammation and IL-1β, TNFα, and IL-6 release, which was inhibited by IL-37tg mice and mice administrated recombinant human IL-37 intranasally (i.n). Moreover, expression of the proliferation-related protein PCNA and migration-related proteins MMP-2, MMP-9, and Vimentin was reduced in lung tissues of IL-37tg mice and mice given recombinant human IL-37 i.n. Abnormal cell contraction, proliferation, and migration of human airway smooth muscle cells (hASMCs) incubated with PM2.5 were also decreased by IL-37 treatment. In addition, IL-37 intervention of hASMCs before PM2.5 incubation decreased cytoplasmic calcium level and expression of PCNA, MMP-2, MMP-9 and Vimentin. Finally, knockdown of the IL-37 receptor IL-1R8 gene eliminated the protective effects of IL-37 in the above responses. We conclude that IL-37 inhibits inflammation activation and disease severity of airway hyperreactivity by PM2.5 induction.
The underlying mechanisms protective function of IL-37 involved in PM2.5-induced airway hyperresponsiveness. PM2.5 induces abnormal cell contraction, proliferation and migration of airway smooth muscle cells (hASMCs) accounting for abnormal bronchial contraction, airway resistance increase and airway hyperresponsiveness. IL-37 inhibits above processes to alleviate airway hyperresponsiveness induced by PM2.5 interacting with IL-1R8. [Display omitted]
•Airway hyperresponsiveness inhibited by IL-37 transgenic mice.•IL-37 alleviated abnormal cell proliferation and migration of human airway smooth muscle cells.•IL-37 decreased cytoplasmic calcium concentration.•IL-37 may be a potential therapeutic target in airway hyperresponsiveness induced by PM2.5.