{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T03:40:49Z","timestamp":1770781249373,"version":"3.50.0"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[1997,8,1]],"date-time":"1997-08-01T00:00:00Z","timestamp":870393600000},"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":[[1997,8]]},"abstract":"<jats:p>Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription.<\/jats:p>","DOI":"10.1128\/iai.65.8.3218-3224.1997","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T19:19:48Z","timestamp":1578338388000},"page":"3218-3224","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":212,"title":["Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45"],"prefix":"10.1128","volume":"65","author":[{"given":"M","family":"Aihara","sequence":"first","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"D","family":"Tsuchimoto","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"H","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"A","family":"Azuma","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"H","family":"Wakebe","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"Y","family":"Ohmoto","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"K","family":"Imagawa","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"M","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"N","family":"Mukaida","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]},{"given":"K","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. m_aihara@research.otsuka.co.jp"}]}],"member":"235","container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.65.8.3218-3224.1997","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.65.8.3218-3224.1997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T09:17:02Z","timestamp":1646471822000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.65.8.3218-3224.1997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1997,8]]}},"alternative-id":["10.1128\/iai.65.8.3218-3224.1997"],"URL":"https:\/\/doi.org\/10.1128\/iai.65.8.3218-3224.1997","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8]]},"assertion":[{"value":"1997-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}