title: Effect of interferon-gamma on hepatic stellate cells stimulated by acetaldehyde.
abstract: OBJECTIVE
  Liver fibrosis in alcoholics has been linked to the oxidation of ethanol to the highly reactive compound acetaldehyde and accumulating evidence has indicated a close link between alcohol and TGF-beta1. Although, it is considered that IFN-gamma inhibits the transcription of matrix, it has not been well defined whether IFN-gamma could inhibit the expression of matrix induced by acetaldehyde in
  
  
  METHODS
  HSC were divided into 5 groups, 4 groups were treated with different doses (0, 1000, 1500, 2000 IU/mL) of IFN-gamma and acetaldehyde (200pM) for 24 and 48 h. For the control group, HSC were treated only with medium. The collagen, alpha-SMA, TGF-beta1, Smad4, Smad7 and TGFbetaRI protein expression in HSC were examined by western blot analysis. 5-Bromo-2'-deoxy-uridine (BrdU) labeling assay was used to determine the effect of IFN-gamma on the proliferation of HSC.
  
  
  RESULTS
  IFN-gamma exhibited a dose-dependent inhibitory effect on a-SMA, collagen type I, collagen type III protein expression in HSC (p<0.01); also IFN-gamma implemented a dose-dependent inhibitory effect on TGF-beta1, Smad4 and especially TGFBRI protein expression in HSC (p<0.01). There was no influence of IFN-gamma on HSC proliferation by BrdU labeling assay.
  
  
  CONCLUSIONS
  The present data indicated that IFN-gamma could inhibit the collagen expression in HSC stimulated by acetaldehyde. IFN-gamma could down-regulate the TGF-beta1, Smad4 and especially TGFbetaRI in HSC after acetaldehyde stimulation. This experiment showed 1000, 1500, 2000 IU/mL IFN-gamma were effective and safe to down-regulate the extracellular matrix induced by acetaldehyde in vitro.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
authors.forename: Ming-hao
authors.initials: MH
authors.lastname: Ha
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Hui-ying
authors.initials: HY
authors.lastname: Rao
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Xue-yan
authors.initials: XY
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Ran
authors.initials: R
authors.lastname: Fei
authors.forename: Hong-song
authors.initials: HS
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Cong
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000199:Actins / Q000037:antagonists & inhibitors; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D010446:Peptide Fragments; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; C069261:interferon gamma (1-39); D007371:Interferon-gamma; D003094:Collagen; D000079:Acetaldehyde