Inhibition of Gas6 promotes crystalline silica‐induced inflammatory response of macrophages via blocking autophagy flux. Issue 8 (19th April 2022)

• Record Type: Journal Article
• Authors: Xie, Yujia; Ma, Jixuan; Xie, Li; Li, Wei; Yang, Meng; Gu, Pei; Zhang, Yingdie; Fan, Lieyang; Wang, Dongming; Chen, Weihong
• Is Part Of: Environmental toxicology. Volume 37:Issue 8(2022)
• Page Start: 1925
• Page End: 1933
• Publication Date: 2022-04-19
• Subjects: autophagy -- crystalline silica -- growth arrest‐specific protein 6 -- inflammatory response -- macrophage; Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.23539
• Languages: English
• ISSNs: 1520-4081

Abstract

Abstract: 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.