N-acetyl-L-cysteine inhibits TGF-beta1-induced profibrotic responses in fibroblasts

Pulm Pharmacol Ther. 2009 Dec;22(6):487-91. doi: 10.1016/j.pupt.2009.04.002. Epub 2009 Apr 22.


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.

MeSH terms

  • Acetylcysteine / pharmacology*
  • Actins / biosynthesis
  • Actins / genetics
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Collagen Type I / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology*
  • Fibronectins / biosynthesis
  • Fibronectins / genetics
  • Fibrosis
  • Humans
  • Rats
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / toxicity*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics


  • Actins
  • Collagen Type I
  • Fibronectins
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • Acetylcysteine