title: Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis.
abstract: BACKGROUND
  Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration.
  
  
  RESULTS
  Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO2 treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO2-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO2-induced increase in cell migration.
  
  
  CONCLUSIONS
  These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO2. CCR2 was also up-regulated in response to SiO2, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO2-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis.
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
authors.affiliation: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, China.
authors.forename: Shencun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Xiaoniu
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Yun
authors.affiliation: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, China.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China. Electronic address: chaojie@seu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D012822:Silicon Dioxide
keywords: CCR2; Fibroblast; MCP-1; MCPIP1; Migration; Silicosis