Inhibition of Gas6 promotes crystalline silica-induced inflammatory response of macrophages via blocking autophagy flux.

Yujia Xie, Jixuan Ma, Li Xie, Wei Li, Meng Yang, Pei Gu, Yingdie Zhang, Lieyang Fan, Dongming Wang, Weihong Chen

Environmental toxicology 2022 Aug

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Inhalation of crystalline silica (CS) can cause silicosis, which is one of the most serious interstitial lung diseases worldwide. Autophagy dysfunction is an essential step in silicosis progression. In this study, we aim to identify the effect of growth arrest-specific protein 6 (Gas6) during autophagy induction and macrophage inflammatory response caused by CS. After RAW 264.7 macrophages exposed to CS, the levels of Gas6 and autophagy markers (p62, Beclin1, and LC3-II/LC3-I) were increased, accompanied with enhanced inflammatory cytokines secretion. Using autophagy activator (rapamycin) repressed, whereas autophagy inhibitor (3-methyladenine) promoted inflammatory cytokines release. Besides, inhibition of Gas6 aggravated CS-induced inflammatory response, and autophagy inhibition facilitated the promoted effect of Gas6 silencing, resulting in elevated expression of inflammatory cytokines. These findings reveal the protective effects of Gas6 and autophagy in macrophages in response to CS exposure, and highlight the autophagy regulated by Gas6 may be a potential prevention target for CS-induced lung inflammatory response. © 2022 Wiley Periodicals LLC.

Citation

Yujia Xie, Jixuan Ma, Li Xie, Wei Li, Meng Yang, Pei Gu, Yingdie Zhang, Lieyang Fan, Dongming Wang, Weihong Chen. Inhibition of Gas6 promotes crystalline silica-induced inflammatory response of macrophages via blocking autophagy flux. Environmental toxicology. 2022 Aug;37(8):1925-1933