@article{oai:u-ryukyu.repo.nii.ac.jp:02005221,
 author = {Takeshima, Eriko and Tomimori, Koh and Teruya, Hiromitsu and Ishikawa, Chie and Senba, Masachika and D' Ambrosio, Daniele and Kinjo, Fukunori and Mimuro, Hitomi and Sasakawa, Chihiro and Hirayama, Toshiya and Fujita, Jiro and Mori, Naoki},
 issue = {4},
 journal = {Infection and immunity},
 month = {Apr},
 note = {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., 論文},
 pages = {1337--1348},
 title = {Helicobacter pylori-Induced Interleukin-12 p40 Expression},
 volume = {77},
 year = {2009}
}