title: MCPIP1 Regulates Alveolar Macrophage Apoptosis and Pulmonary Fibroblast Activation After in vitro Exposure to Silica.
abstract: 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.
  
  
  
  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.
  
  
  
  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: *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
authors: Xingang
authors: X
authors: Wang
authors: *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
authors: Yuxia
authors: Y
authors: Zhang
authors: *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
authors: Wei
authors: W
authors: Zhang
authors: *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.
authors: Haijun
authors: H
authors: Liu
authors: *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
authors: Zewei
authors: Z
authors: Zhou
authors: *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
authors: Xiaoniu
authors: X
authors: Dai
authors: *Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
authors: Yusi
authors: Y
authors: Cheng
authors: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, China.
authors: Shencun
authors: S
authors: Fang
authors: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, China.
authors: Yingming
authors: Y
authors: Zhang
authors: 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.
authors: Honghong
authors: H
authors: Yao
authors: *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.
authors: Jie
authors: J
authors: Chao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019899:Paracrine Communication; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D012260:Ribonucleases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection
chemical_list: D017077:Culture Media, Conditioned; D012822:Silicon Dioxide; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D012260:Ribonucleases; C000616614:Zc3h12a protein, rat
keywords: MCPIP1; apoptosis.; fibroblast; macrophage; silicosis