TNFR1/Phox Interaction and TNFR1 Mitochondrial Translocation Thwart Silica-Induced Pulmonary Fibrosis

摘要: Macrophages play a fundamental role in innate immunity and the pathogenesis of silicosis. Phagocytosis silica particles is associated with generation reactive oxygen species (ROS), secretion cytokines, such as TNF, cell death that contribute to silica-induced lung disease. In macrophages, ROS production executed primarily by activation NADPH oxidase (Phox) mitochondrial (mtROS); however, relative contribution unclear, effects on macrophage function fate are unknown. this study, we used primary human mouse macrophages (C57BL/6, BALB/c, p47phox−/−) lines (RAW 264.7 IC21) investigate Phox mtROS injury. We demonstrate reduced p47phox expression IC21 linked enhanced generation, cardiolipin oxidation, accumulation hydrolysis products, culminating death. also observed p47phox−/− mice exhibit increased inflammation fibrosis following exposure. Silica induces interaction between TNFR1 RAW macrophages. Moreover, mitochondria decreased survival silica. These results identify TNFR1/Phox key event silicosis prevents formation reduces apoptosis.