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Inhibitory effects of interferons on pancreatic stellate cell activation

World Journal of Gastroenterology 2006年第6期12卷 896-901页

作者： Jan-TidoBaumert GiselaSparmann J rgEmmrich stefanliebe RobertJaster Department of Me-dicine Division of GastroenterologyMedical FacultyUniversity of RostockE-Heydemann-Str.618057 Rostock Germany

AIM： To analyze and to compare the effects of interferon （IFN）-α, IFN-β, and IFN-γ on pancreatic stellate cell （PSC） activation/n vitro and to elucidate the molecular basis of IFN action. METHODS： PSCs were isolated from rat＇s pancreatic tissue, cultured and stimulated with recombinant rat IFNs. Cell proliferation and collagen synthesis were assessed by measuring the incorporation of 5-bromo-2＇ -deoxyuridine （BrdU） into DNA and [^3H]-proline into acetic acid-soluble proteins, respectively. Apoptotic ceils were determined by FACS analysis （sub-G1 peak method）. Exhibition of the myofibroblastic PSC phenotype was monitored by immunoblot analysis of （α-smooth muscle actin （α-SMA） expression. To assess the activation of signal transducer and activator of transcription （STAT）, Western blots using phospho- STAT-specific antibodies were performed. In studies on STAT1 function, expression of the protein was inhibited by siRNA. RESULTS： IFN-β and IFN-γ, but not IFN-α significantly diminished PSC proliferation and collagen synthesis. IFN-γ, was the only IFN that clearly inhibited α-SMA expression. Under the experimental conditions used, no enhanced rate of apoptotic cell death was observed in response to any IFN treatment. IFN-β and IFN-γ, induced a strong increase of STAT1 and STAT3 tyrosine phosphorylation, while the effect of IFN-α was much weaker. Inhibition of STAT1 expression with siRNA was associated with a significantly reduced growth-inhibitory effect of IFN-γ. CONCLUSION： IFN-β and particularly IFN-γ, display inhibitory effects on PSC activation in vitro and should be tested regarding their in vitro efficiency. Growth inhibition by IFN-γ action requires STAT1.

关键词： Interferons Pancreatic stellate cell Apoptosis

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