Neutralization of interleukin-11 attenuates silica particles-induced pulmonary inflammation and fibrosis in vivo  

作　　者：Jixuan Ma Yujia Xie Yiju Xu Pei Gu Yingdie Zhang Lieyang Fan Yun Zhou Haijiao Wang Ting Zhou Jintong He Dongming Wang Weihong Chen 

机构地区：[1]Department of Occupational&Environmental Health,School of Public Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Key Laboratory of Environment and Health,Ministry of Education&Ministry of Environmental Protection,and State Key Laboratory of Environmental Health(Incubating),School of Public Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [3]State Key Laboratory of Respiratory Disease,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou 511436,China [4]National Center of Occupational Safety and Health,National Health Commission,Beijing 102300,China [5]Department of Occupational and Environmental Health,School of Public Health,Medical College,Wuhan University of Science and Technology,Wuhan 430065,China [6]Zhuhai Center for Chronic Disease Control,Zhuhai 519000,China

出　　处：《Journal of Environmental Sciences》2023年第4期772-783,共12页环境科学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos. 81803205 and 81872593);the China Postdoctoral Science Foundation (No. 2019T120665);the Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology (No. OHIC_(2)020G01);the Fundamental Research Funds for the Central Universities (No. 2020kfy XJJS005);the Open Projects Program of Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment (No. 2017B030314152)。

摘　　要：Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.

关 键 词：Silica particles INFLAMMATION FIBROSIS INTERLEUKIN-11 SILICOSIS 

分 类 号：X503.1[环境科学与工程—环境工程] R563[医药卫生—呼吸系统]