title: Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes.
abstract: OBJECTIVE
  Heme oxygenase-1 (HO-1) can be induced by various stimuli, one of which is interleukin-6 (IL-6). Therefore, the aim of this study was to elucidate the molecular mechanisms responsible for IL-6-dependent HO-1 induction in the liver.
  
  
  METHODS
  The IL-6-dependent HO-1 regulation in rat primary hepatocytes and HepG2 hepatoma cells was studied by Northern and Western blot analyses, HO-1 promoter reporter gene assays and EMSA.
  
  
  RESULTS
  The HO-1 expression was transcriptionally induced by IL-6 in a time- and dose-dependent manner. Activation of signal transducers and activators of transcription (STAT) factors by the IL-6 receptor was crucial for HO-1 induction. By contrast, negative regulation of HO-1 expression appeared to be mediated through the SH2-domain-containing tyrosine phosphatase-2 (SHP2)/ suppressors of cytokine signaling-3 (SOCS3) binding site within the gp130 IL-6 receptor subunit. Among the three putative STAT binding elements (SBE) in the HO-1 promoter, only the distal one was functional and when deleted, the remaining Luc induction was completely obliterated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.
  
  
  CONCLUSIONS
  The HO-1 SBE3 mediates HO-1 gene induction by IL-6 mainly via activation of the Jak/STAT pathway.
authors.affiliation: Abteilung Gastroenterologie und Endokrinologie, Uniklinikum, Georg-August-Universität Göttingen, D-37075 Göttingen, Germany.
authors.forename: Kyrylo
authors.initials: K
authors.lastname: Tron
authors.forename: Anatoly
authors.initials: A
authors.lastname: Samoylenko
authors.forename: Gernot
authors.initials: G
authors.lastname: Musikowski
authors.forename: Fritz
authors.initials: F
authors.lastname: Kobe
authors.forename: Stephan
authors.initials: S
authors.lastname: Immenschuh
authors.forename: Fred
authors.initials: F
authors.lastname: Schaper
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.forename: Thomas
authors.initials: T
authors.lastname: Kietzmann
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D015533:Transcriptional Activation
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat