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Title :Helicobacter pylori-Induced Interleukin-12 p40 Expression
Authors :Takeshima, Eriko
Tomimori, Koh
Teruya, Hiromitsu
Ishikawa, Chie
Senba, Masachika
D' Ambrosio, Daniele
Kinjo, Fukunori
Mimuro, Hitomi
Sasakawa, Chihiro
Hirayama, Toshiya
Fujita, Jiro
Mori, Naoki
Issue Date :Apr-2009
Abstract :Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that promotes the development of T-helper lymphocyte 1 (Th1). Chronic gastritis induced by Helicobacter pylori is considered a Th1-mediated process. IL-12 levels in gastric biopsy samples of H. pylori-infected patients are higher than in those of uninfected individuals, but the cellular source of IL-12 remains elusive. IL-12 staining was detected in mucosal epithelial cells, lymphocytes, and macrophages in specimens of patients with H. pylori-positive gastritis. Therefore, we investigated IL-12 p40 mRNA induction by H. pylori in gastric epithelial cells and T cells. Although cag pathogenicity island (PAI)-positive H. pylori induced IL-12 p40 mRNA expression, an isogenic mutant of the cag PAI failed to induce it in both cell types. Supernatants from H. pylori cultures and H. pylori VacA induced IL-12 p40 mRNA expression in T cells but not in epithelial cells. The activation of the IL-12 p40 promoter by H. pylori was mediated through NF-κB. The transfection of IκB kinase and NF-κB-inducing kinase dominant-negative mutants inhibited H. pylori-induced IL-12 p40 activation. Inhibitors of NF-κB, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and Hsp90 suppressed H. pylori- and VacA-induced IL-12 p40 mRNA expression. The results indicate that H. pylori induces IL-12 p40 expression by the activation of NF-κB, phosphatidylinositol 3-kinase, and p38 mitogen-activated protein kinase. Hsp90 is also a crucial regulator of H. pylori-induced IL-12 p40 expression. In addition to the cag PAI, VacA might be relevant in the induction of IL-12 expression and a Th1-polarized response only in T cells.
URL :http://iai.asm.org/cgi/content/abstract/77/4/1337
Type Local :雑誌掲載論文
ISSN :0019-9567
Publisher :American Society for Microbiology
URI :http://hdl.handle.net/20.500.12000/14407
Citation :Infection and immunity Vol.77 no.4 p.1337 -1348
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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