| 19393328 |
Sugiura H, Ichikawa T, Liu X, Kobayashi T, Wang XQ, Kawasaki S, Togo S, Kamio K, Mao L, Ann Y, Ichinose M, Rennard SI: N-acetyl-L-cysteine inhibits TGF-beta1-induced profibrotic responses in fibroblasts. Laryngoscope. 2008 Jan;118(1):94-8.
BACKGROUND: Excessive production of TGF-beta (1) plays a key role in the tissue remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-beta (1) has been reported to decrease the intracellular glutathione level and stimulate the production of reactive oxygen species. OBJECTIVES: The aim of this study was to evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-beta (1)-mediated tissue remodeling in fibroblasts or modulate the production of fibronectin and vascular endothelial growth factor (VEGF) which are believed to be important mediators of tissue repair and remodeling. METHODS: To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC on the TGF-beta (1)-mediated contraction of floating gels and the TGF-beta (1)-induced mediator production. In addition, the effect of NAC on the TGF-beta (1)-induced differentiation to myofibroblasts was evaluated by assessing alpha-smooth muscle actin (alpha-SMA) expression. RESULTS: NAC significantly abolished the TGF-beta (1)-augmented gel contraction (at 3mM, gel size 63.4+/-2.6% vs. 39.1+/-4.1%; p <0.01) compared with control in a concentration-dependent manner. NAC also significantly inhibited the TGF-beta (1)-augmented fibronectin (p <0.01) and VEGF (p <0.01) production in the media of both the three-dimensional gel and monolayer culture. Furthermore, NAC reversed the TGF-beta (1)-stimulated alpha-SMA expression (p <0.01). CONCLUSION: These results suggest that NAC can affect the TGF-beta (1)-induced tissue remodeling or fibrotic process in vitro. |
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