Xingang Wang1, Yuxia Zhang2, Wei Zhang2, Haijun Liu3, Zewei Zhou1, Xiaoniu Dai2, Yusi Cheng2, Shencun Fang4, Yingming Zhang4, Honghong Yao5, Jie Chao6. 1. *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China. 2. *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China. 3. *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009, China. 4. Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, China. 5. Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China. 6. *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China, Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China chaojie@seu.edu.cn.
Abstract
BACKGROUND: Silicosis is a fatal and fibrotic pulmonary disease caused by the inhalation of silica. After arriving at the alveoli, silica is ingested by alveolar macrophages (AMOs), in which monocyte chemotactic protein-induced protein 1 (MCPIP1) plays an essential role in controlling macrophage-mediated inflammatory responses. However, the mechanism of action of MCPIP1 in silicosis is poorly understood. METHODS: Primary rat AMOs were isolated and treated with SiO2 (50 µg/cm(2)). MCPIP1 and AMO activation/apoptosis markers were detected by immunoblotting. MCPIP1 was down-regulated using siRNA in AMOs. The effects of AMOs on fibroblast activation and migration were evaluated using a gel contraction assay, a scratch assay, and a nested collagen matrix migration model. RESULTS: After exposure to SiO2, MCPIP1 was significantly increased in rat AMOs. Activation and apoptosis markers in AMOs were up-regulated after exposure to SiO2 Following siRNA-mediated silencing of MCPIP1 mRNA, the markers of AMO activation and apoptosis were significantly decreased. Rat pulmonary fibroblasts (PFBs) cultured in conditional medium from AMOs treated with MCPIP1 siRNA and SiO2 showed significantly less activation and migration compared with those cultured in conditional medium from AMOs treated with control siRNA and SiO2 CONCLUSION: Our data suggest a vital role for MCPIP1 in AMO apoptosis and PFB activation/migration induced by SiO2.
BACKGROUND: Silicosis is a fatal and fibrotic pulmonary disease caused by the inhalation of silica. After arriving at the alveoli, silica is ingested by alveolar macrophages (AMOs), in which monocyte chemotactic protein-induced protein 1 (MCPIP1) plays an essential role in controlling macrophage-mediated inflammatory responses. However, the mechanism of action of MCPIP1 in silicosis is poorly understood. METHODS: Primary rat AMOs were isolated and treated with SiO2 (50 µg/cm(2)). MCPIP1 and AMO activation/apoptosis markers were detected by immunoblotting. MCPIP1 was down-regulated using siRNA in AMOs. The effects of AMOs on fibroblast activation and migration were evaluated using a gel contraction assay, a scratch assay, and a nested collagen matrix migration model. RESULTS: After exposure to SiO2, MCPIP1 was significantly increased in rat AMOs. Activation and apoptosis markers in AMOs were up-regulated after exposure to SiO2 Following siRNA-mediated silencing of MCPIP1 mRNA, the markers of AMO activation and apoptosis were significantly decreased. Rat pulmonary fibroblasts (PFBs) cultured in conditional medium from AMOs treated with MCPIP1 siRNA and SiO2 showed significantly less activation and migration compared with those cultured in conditional medium from AMOs treated with control siRNA and SiO2 CONCLUSION: Our data suggest a vital role for MCPIP1 in AMO apoptosis and PFB activation/migration induced by SiO2.
Authors: Bethany B Moore; Marc Peters-Golden; Paul J Christensen; Vibha Lama; William A Kuziel; Robert Paine; Galen B Toews Journal: Am J Physiol Lung Cell Mol Physiol Date: 2002-10-04 Impact factor: 5.464