title: Inhibitory effects of interferons on pancreatic stellate cell activation.
abstract: OBJECTIVE
  To analyze and to compare the effects of interferon (IFN)-alpha, IFN-beta, and IFN-gamma on pancreatic stellate cell (PSC) activation in 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 cells were determined by FACS analysis (sub-G1 peak method). Exhibition of the myofibroblastic PSC phenotype was monitored by immunoblot analysis of alpha-smooth muscle actin (alpha- 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-beta and IFN-gamma but not IFN-alpha significantly diminished PSC proliferation and collagen synthesis. IFN-gamma was the only IFN that clearly inhibited alpha-SMA expression. Under the experimental conditions used, no enhanced rate of apoptotic cell death was observed in response to any IFN treatment. IFN-beta and IFN-gamma induced a strong increase of STAT1 and STAT3 tyrosine phosphorylation, while the effect of IFN-alpha was much weaker. Inhibition of STAT1 expression with siRNA was associated with a significantly reduced growth-inhibitory effect of IFN-gamma.
  
  
  CONCLUSIONS
  IFN-beta and particularly IFN-gamma display inhibitory effects on PSC activation in vitro and should be tested regarding their in vitro efficiency. Growth inhibition by IFN-gamma action requires STAT1.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Medical Faculty, University of Rostock, 18057 Rostock, Germany.
authors.forename: Jan-Tido
authors.initials: JT
authors.lastname: Baumert
authors.forename: Gisela
authors.initials: G
authors.lastname: Sparmann
authors.forename: Jorg
authors.initials: J
authors.lastname: Emmrich
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebe
authors.forename: Robert
authors.initials: R
authors.lastname: Jaster
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D007372:Interferons / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D007372:Interferons