title: Transforming growth factor-β1 suppresses the up-regulation of matrix metalloproteinase-2 by lung fibroblasts in response to tumor necrosis factor-α.
abstract: Exposed to inflammatory factors or cytokines, fibroblasts appear to play additional roles beyond the deposition of extracellular matrix. It has been reported that tumor necrosis factor-α (TNF-α) induces the production of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-β1 (TGF-β1) in fibroblasts. In this study, we demonstrated that the active MMP-2 secreted by lung fibroblasts reached the peak level at 12 hours after TNF-α treatment, whereas, by adding anti-TGF-β1 antibody in the culture medium, the MMP-2 production in response to TNF-α was maintained at high levels after 24 hours of treatment. We also confirmed that TNF-α induced up-regulation of active TGF-β1 and exogenous TGF-β1 induced down-regulation of MMP-2 synthesis in lung fibroblasts. Moreover, an increased MMP-2 level was observed in a rat model with pulmonary inflammation and fibrosis induced by bleomycin-A5. This revealed that MMP-2 in the lung reached the peak level when TNF-α reached the peak level at the 7th day, and then MMP-2 decreased along with an increase in the TGF-β1 level. Taken together, our results demonstrate that TNF-α induced an increase of MMP-2 and TGF-β1 in lung fibroblasts, and the TGF-β1 attenuated the up-regulation of MMP-2. This suggests that MMP-2 secreted from fibroblasts modulated by TNF-α/TGF-β1 might play an important role in pulmonary inflammation and fibrosis.
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Cai
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Ma
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2