| 18705328 |
Ha MH, Wei L, Rao HY, Liu F, Wang XY, Feng B, Fei R, Chen HS, Cong X: Effect of interferon-gamma on hepatic stellate cells stimulated by acetaldehyde. Hepatogastroenterology. 2008 May-Jun;55(84):1059-65.
BACKGROUND/AIMS: 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 METHODOLOGY: 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. |
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