1. MCPIP1 Regulates Alveolar Macrophage Apoptosis and Pulmonary Fibroblast Activation Afterin vitroExposure to Silica
- Author
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Yusi Cheng, Jie Chao, Yuxia Zhang, Yingming Zhang, Shencun Fang, Honghong Yao, Zewei Zhou, Xingang Wang, Xiaoniu Dai, Haijun Liu, and Wei Zhang
- Subjects
Male ,0301 basic medicine ,Time Factors ,Silicosis ,Apoptosis ,Transfection ,Toxicology ,Rats, Sprague-Dawley ,03 medical and health sciences ,Ribonucleases ,Cell Movement ,Macrophages, Alveolar ,Paracrine Communication ,Animals ,Medicine ,Gene silencing ,Phosphorylation ,Fibroblast ,Lung ,Cells, Cultured ,business.industry ,Monocyte ,Fibroblasts ,Silicon Dioxide ,medicine.disease ,Molecular biology ,A Role for Monocyte Chemotactic Protein-Induced Protein 1 in Alveolar Macrophagae Response to Silica ,030104 developmental biology ,medicine.anatomical_structure ,Mechanism of action ,Culture Media, Conditioned ,Immunology ,Alveolar macrophage ,RNA Interference ,Collagen ,Mitogen-Activated Protein Kinases ,medicine.symptom ,business ,Proto-Oncogene Proteins c-akt ,Signal Transduction - 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/cm2). 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.
- Published
- 2016
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