Blockage of HSP 90 modulates Helicobacter pylori-induced IL-8 productions through the inactivation of transcriptional factors of AP-1 and NF-kappaB.
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.
Yeo
Marie
M
Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Park
Hyun-kyung
HK
Lee
Ki-myung
KM
Lee
Kwang Jae
KJ
Kim
Jin Hong
JH
Cho
Sung Won
SW
Hahm
Ki-baik
KB
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
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