title: Lipopolysaccharides may aggravate apoptosis through accumulation of autophagosomes in alveolar macrophages of human silicosis.
abstract: Silica dust mainly attacks alveolar macrophages (AMs) and increases the apoptosis of AMs in silicosis patients. However, it is still unclear whether autophagy is affected. Autophagy mainly has defensive functions in response to stress, contributing to cell survival in adverse conditions, and conversely it has also been implicated in cell death. Lipopolysaccharide (LPS) induces autophagy and apoptosis in macrophages. The role of LPS in autophagy and apoptosis in AMs of silicosis patients is unknown. In this study, we collected AMs from 53 male workers exposed to silica and divided them into an observer (control) group, and stage I, II and III patient groups. We found increased levels of LC3B, SQSTM1/p62 and BECN1，whereas the phosphorylation of MTOR，and levels of LAMP2, TLR4, MYD88, TICAM1, as well as the number of lysosomes decreased with the development of silicosis. LPS stimulation triggered autophagy and increased levels of SQSTM1 in AMs. The autophagy inhibitor, 3-methyladenine (3MA), inhibited LPS-induced apoptosis in the AMs of silicosis patients. Moreover, 3MA reversed the LPS-induced decrease in BCL2 and the increase in BAX and CASP3 levels in AMs. These results suggest that autophagosomes accumulate in AMs during silicosis progression. LPS can induce the formation of autophagosomes through a TLR4-dependent pathway, and LPS may exacerbate the apoptosis in AMs. Blockade of the formation of autophagosomes may inhibit LPS-induced apoptosis via the intrinsic apoptotic pathway in AMs. These findings describe novel mechanisms that may lead to new preventive and therapeutic strategies for pulmonary fibrosis.
authors.affiliation: a School of Public Health; China Medical University ; Shenyang , China.|b School of Public Health; North China University of Science and Technology ; Tangshan , China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: b School of Public Health; North China University of Science and Technology ; Tangshan , China.
authors.forename: Juxiang
authors.initials: J
authors.lastname: Yuan
authors.affiliation: c School of Public Health; Xinxiang Medical University ; Xinxiang , China.
authors.forename: Sanqiao
authors.initials: S
authors.lastname: Yao
authors.affiliation: b School of Public Health; North China University of Science and Technology ; Tangshan , China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: d Department of Pneumoconiosis ; Beidaihe Sanitarium for China Coal Miners ; Beidaihe , China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: e Heart Institute; North China University of Science and Technology ; Tangshan , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: e Heart Institute; North China University of Science and Technology ; Tangshan , China.
authors.forename: Jinkun
authors.initials: J
authors.lastname: Xi
authors.affiliation: e Heart Institute; North China University of Science and Technology ; Tangshan , China.
authors.forename: Zhelong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: a School of Public Health; China Medical University ; Shenyang , China.
authors.forename: Dong
authors.initials: D
authors.lastname: Weng
authors.affiliation: a School of Public Health; China Medical University ; Shenyang , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects*; D012829:Silicosis / Q000188:drug therapy
chemical_list: D051017:Apoptosis Regulatory Proteins; D008070:Lipopolysaccharides; D053148:Caspase 3
keywords: LPS; TLR4; alveolar macrophages; apoptosis; autophagic degradation; autophagosome; autophagy; lysosome; silicosis