Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori.

نویسندگان

  • Hong Lu
  • Jeng Yih Wu
  • Takahiko Kudo
  • Tomoyuki Ohno
  • David Y Graham
  • Yoshio Yamaoka
چکیده

The regulation of Helicobacter pylori induced interleukin (IL)-6 in the gastric epithelium remains unclear. Primary gastric epithelial cells and MKN28 cells were cocultured with H. pylori and its isogenic cag pathogenicity island (PAI) mutant and/or oipA mutants. H. pylori infection-induced IL-6 mRNA expression and IL-6 protein production, which was further enhanced by the cag PAI and OipA. Luciferase reporter gene assays and electrophoretic mobility shift assays showed that full IL-6 transcription required binding sites for nuclear factor-kappaB (NF-kappaB), cAMP response element (CRE), CCAAT/enhancer binding protein (C/EBP), and activator protein (AP)-1. The cag PAI and OipA were involved in binding to NF-kappaB, AP-1, CRE, and C/EBP sites. The cag PAI activated the extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) pathways; OipA activated the p38 pathway. Transfection of dominant negative G-protein confirmed roles for Raf, Rac1, and RhoA in IL-6 induction. Overall, the cag PAI-related IL-6 signal transduction pathway involved the Ras/Raf/MEK1/2/ERK/AP-1/CRE pathway and the JNK/AP-1/CRE pathway; the OipA-related pathway is p38/AP-1/CRE and both the cag PAI and OipA appear to be involved in the RhoA/Rac1/NF-kappaB pathway. Combination of different pathways by the cag PAI and OipA will lead to the maximum IL-6 induction.

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عنوان ژورنال:
  • Molecular biology of the cell

دوره 16 10  شماره 

صفحات  -

تاریخ انتشار 2005