title: Blockage of HSP 90 modulates Helicobacter pylori-induced IL-8 productions through the inactivation of transcriptional factors of AP-1 and NF-kappaB.
abstract: Helicobacter pylori infection leads to significant inflammations in the gastric mucosa, which is closely associated with development of gastric cancer. Heat shock protein 90 (HSP 90) has been revealed to be critical for intracellular signaling that participates in inflammatory response as well as carcinogenesis. In this study, we investigated a regulatory role of HSP 90 in H. pylori-induced IL-8 production. Our results showed that H. pylori stimulated significant phosphorylation of HSP 90 and the phosphorylation was diminished by administration of HSP 90 inhibitor, geldanamycin (GA). Treatment of GA completely inhibited H. pylori-induced IL-8 production due to deactivation of ERK1/2 and NF-kappaB. These results subsequently lead to inactivation of AP-1 and NF-kappaB, which are known to be major transcriptional factors of IL-8. Our data provide important insights that HSP 90 is involved as a crucial regulator in H. pylori-induced IL-8 production and its inhibitor could be potentially used for the inhibition of H. pylori-provoked inflammation.
authors.affiliation: Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Marie
authors.initials: M
authors.lastname: Yeo
authors.forename: Hyun-kyung
authors.initials: HK
authors.lastname: Park
authors.forename: Ki-myung
authors.initials: KM
authors.lastname: Lee
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Lee
authors.forename: Jin Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Ki-baik
authors.initials: KB
authors.lastname: Hahm
mesh_terms: D016227:Benzoquinones; D002460:Cell Line; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D047029:Lactams, Macrocyclic; D016328:NF-kappa B / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D016209:Interleukin-8; D047029:Lactams, Macrocyclic; D016328:NF-kappa B; D011809:Quinones; D018808:Transcription Factor AP-1; C001277:geldanamycin