title: N-acetyl-L-cysteine inhibits TGF-beta1-induced profibrotic responses in fibroblasts.
abstract: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  These results suggest that NAC can affect the TGF-beta(1)-induced tissue remodeling or fibrotic process in vitro.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan. sugiura@wakayama-med.ac.jp
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Xing Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: Shin
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Togo
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kamio
authors.forename: Lijun
authors.initials: L
authors.lastname: Mao
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Ann
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology*; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D005355:Fibrosis; D006801:Humans; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000111:Acetylcysteine