Ting Zhou1,2,3, Qimei Yu1,2, Hui Lin1,2, Zhenyu Wang2,4, Guoqing Fu1,2, Lu Lei1,2, Yuqin Shi1,2, Ling Zhang1,2, Lingzhi Qin5, Yuewei Liu6. 1. Department of Occupational and Environmental Health, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, 430065, Hubei, China. 2. Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, 430065, Hubei, China. 3. Department of Physiology, Wayne State University, Detroit, MI, 48201, USA. 4. Department of Basic Medicine, Medical College, Wuhan University of Science and Technology, Wuhan, 430065, Hubei, China. 5. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. qinlingzhi@163.com. 6. Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China. liuyuewei@mail.sysu.edu.cn.
Abstract
BACKGROUND: Prolonged exposure to crystalline silica leads to persistent pulmonary inflammation and progressive fibrosis. Connective tissue growth factor (CTGF) has emerged as a potent proinflammatory and profibrotic regulator to participate in a variety of chronic inflammatory diseases. However, the role of CTGF in silica-induced pulmonary inflammation remains poorly understood. METHODS: To explore the effect of CTGF on inflammatory responses caused by silica particles, human bronchial epithelial cells (16HBE) were transfected with CTGF siRNA and exposed to silica particles at concentrations of 0, 12.5, 25, 50, 100 μg/ml for 48 h. Intracellular CTGF mRNA and protein expressions were determined by RT-PCR and Western blotting, respectively. The levels of inflammatory cytokines including IL-8, TNF-α, IL-6, IL-1β, IL-17A and TGF-β1 were measured by ELISA kits. RESULTS: Silica particles induce significantly elevated intracellular CTGF mRNA expression in 16HBE cells in a dose-dependent manner when compared with blank control group (P < 0.05). The secretions of IL-8, TNF-α, IL-6 and IL-17A were also significantly increased by silica particles (P < 0.05). After exposure to 25 or 50 μg/ml silica particles, the expression of intracellular CTGF mRNA was significantly inhibited in 16HBE cells when transfected with CTGF siRNA (P < 0.05). The secreted levels of IL-8, TNF-α, IL-6 and IL-17A induced by silica particles were also significantly lower from CTGF siRNA-transfected cells than that from normal 16HBE cells (P < 0.05). CONCLUSION: Inhibition of CTGF gene attenuates silica-induced inflammatory responses in bronchial epithelial cells, suggesting that CTGF could be a pivotal regulator in the development of silica-induced inflammation.
BACKGROUND: Prolonged exposure to crystalline silica leads to persistent pulmonary inflammation and progressive fibrosis. Connective tissue growth factor (CTGF) has emerged as a potent proinflammatory and profibrotic regulator to participate in a variety of chronic inflammatory diseases. However, the role of CTGF in silica-induced pulmonary inflammation remains poorly understood. METHODS: To explore the effect of CTGF on inflammatory responses caused by silica particles, human bronchial epithelial cells (16HBE) were transfected with CTGF siRNA and exposed to silica particles at concentrations of 0, 12.5, 25, 50, 100 μg/ml for 48 h. Intracellular CTGF mRNA and protein expressions were determined by RT-PCR and Western blotting, respectively. The levels of inflammatory cytokines including IL-8, TNF-α, IL-6, IL-1β, IL-17A and TGF-β1 were measured by ELISA kits. RESULTS:Silica particles induce significantly elevated intracellular CTGF mRNA expression in 16HBE cells in a dose-dependent manner when compared with blank control group (P < 0.05). The secretions of IL-8, TNF-α, IL-6 and IL-17A were also significantly increased by silica particles (P < 0.05). After exposure to 25 or 50 μg/ml silica particles, the expression of intracellular CTGF mRNA was significantly inhibited in 16HBE cells when transfected with CTGF siRNA (P < 0.05). The secreted levels of IL-8, TNF-α, IL-6 and IL-17A induced by silica particles were also significantly lower from CTGF siRNA-transfected cells than that from normal 16HBE cells (P < 0.05). CONCLUSION: Inhibition of CTGF gene attenuates silica-induced inflammatory responses in bronchial epithelial cells, suggesting that CTGF could be a pivotal regulator in the development of silica-induced inflammation.
Authors: Andrea K Hubbard; Cynthia R Timblin; Arti Shukla; Mercedes Rincón; Brooke T Mossman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2002-05 Impact factor: 5.464
Authors: Michelangelo Di Giuseppe; Federica Gambelli; Gary W Hoyle; Giuseppe Lungarella; Sean M Studer; Thomas Richards; Sam Yousem; Ken McCurry; James Dauber; Naftali Kaminski; George Leikauf; Luis A Ortiz Journal: PLoS One Date: 2009-05-25 Impact factor: 3.240