Analysis of differentiation system in the stomach by the immune response to Helicobactor pylori infection

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: IMATANI Akira Tohoku University, Center for the Advancement of Higher Education, Assistant professor, 高等教育開発推進センター, 助手 (30333876)
• Co-Investigator(Kenkyū-buntansha): IIJIMA Katunori Hospital, Assistant professor, 病院・助手 (60375003) ; OHARA Shuichi Center for the Advancement of Higher Education, Associate professor, 高等教育開発推進センター, 助教授 (40223929)
• Project Period (FY): 2005 – 2006
• Keywords: differentiation / regulation of expression / signaling / immunology / stomach

Research Abstract

Helicobacter pylori (H.pylori) infection induces the 'switch of differentiation' from gastric oxytinc glands to atrophy and intestinal metaplasia(IM), which are a risk factor in gastric cancer development. This switch may be induced by host immune response to it. But little is known about the molecular mechanism of this 'switch of differentiation'. In this project, we have clarified one of the mechanisms through a homeobox gene Cdx2 and SRY-related HMG box gene Sox2. Cdx2, which can be developed IM, was induced by the H.pylori stimulation through phospho-AKT/AKT / NF-κB signaling pathway in gastric cell lines, AGS and GCIY. On the other hand, when stimulating with IFN-y, TNF-a, IL-1β and IL-4 in gastric cell lines, the expression level of Sox2 increased in both AGS and MKN45 after the stimulation with IL-4, a Th2-related cytokine, through STAT6 signaling. But little changes of Sox2 expression were observed after the treatment with IFN-γ, IL-1β, or TNF-a, Thl-related cytokine. Moreover, H. pylori infection and IFN-γ stimulation dose-dependently inhibited IL-4-induced expression of Sox2. The inhibition of Sox2 expression by siRNA transfection substantially increased the expression of Cdx2. Therefore, the down-regulation of Sox2 by H.pylori infection and Thl-dominant host immune response to it may promote gastric atrophy and intestinal metaplasia in the view of 'switch of differentiation'.