{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:55:01Z","timestamp":1767167701687,"version":"build-2238731810"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    is considered a Th1-mediated process. IL-12 levels in gastric biopsy samples of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -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\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -positive gastritis. Therefore, we investigated IL-12 p40 mRNA induction by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    in gastric epithelial cells and T cells. Although\n                    <jats:italic>cag<\/jats:italic>\n                    pathogenicity island (PAI)-positive\n                    <jats:italic>H. pylori<\/jats:italic>\n                    induced IL-12 p40 mRNA expression, an isogenic mutant of the\n                    <jats:italic>cag<\/jats:italic>\n                    PAI failed to induce it in both cell types. Supernatants from\n                    <jats:italic>H. pylori<\/jats:italic>\n                    cultures and\n                    <jats:italic>H. pylori<\/jats:italic>\n                    VacA induced IL-12 p40 mRNA expression in T cells but not in epithelial cells. The activation of the IL-12 p40 promoter by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    was mediated through NF-\u03baB. The transfection of I\u03baB kinase and NF-\u03baB-inducing kinase dominant-negative mutants inhibited\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -induced IL-12 p40 activation. Inhibitors of NF-\u03baB, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and Hsp90 suppressed\n                    <jats:italic>H. pylori<\/jats:italic>\n                    - and VacA-induced IL-12 p40 mRNA expression. The results indicate that\n                    <jats:italic>H. pylori<\/jats:italic>\n                    induces IL-12 p40 expression by the activation of NF-\u03baB, phosphatidylinositol 3-kinase, and p38 mitogen-activated protein kinase. Hsp90 is also a crucial regulator of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -induced IL-12 p40 expression. In addition to the\n                    <jats:italic>cag<\/jats:italic>\n                    PAI, VacA might be relevant in the induction of IL-12 expression and a Th1-polarized response only in T cells.\n                  <\/jats:p>","DOI":"10.1128\/iai.01456-08","type":"journal-article","created":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T20:45:10Z","timestamp":1233261910000},"page":"1337-1348","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["<i>Helicobacter pylori<\/i>\n                    -Induced Interleukin-12 p40 Expression"],"prefix":"10.1128","volume":"77","author":[{"given":"Eriko","family":"Takeshima","sequence":"first","affiliation":[{"name":"Divisions of Molecular Virology and Oncology"},{"name":"Control and Prevention of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koh","family":"Tomimori","sequence":"additional","affiliation":[{"name":"Divisions of Molecular Virology and Oncology"},{"name":"Control and Prevention of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromitsu","family":"Teruya","sequence":"additional","affiliation":[{"name":"Divisions of Molecular Virology and Oncology"},{"name":"Control and Prevention of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chie","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Divisions of Molecular Virology and Oncology"},{"name":"Graduate School of Medicine, Division of Child Health and Welfare, Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masachika","family":"Senba","sequence":"additional","affiliation":[{"name":"Departments of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"D'Ambrosio","sequence":"additional","affiliation":[{"name":"BioXell SpA, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fukunori","family":"Kinjo","sequence":"additional","affiliation":[{"name":"Department of Endoscopy, University Hospital, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitomi","family":"Mimuro","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihiro","family":"Sasakawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiya","family":"Hirayama","sequence":"additional","affiliation":[{"name":"Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Control and Prevention of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Mori","sequence":"additional","affiliation":[{"name":"Divisions of Molecular Virology and Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1365-2958.1998.00770.x","volume":"28","year":"1998","unstructured":"Akopyants, N. 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