RT Journal Article SR Electronic(1) A1 Takenaka, Ryuta A1 Yokota, Kenji A1 Ayada, Kiyoshi A1 Mizuno, Motowo A1 Zhao, Ying A1 Fujinami, Yoshihito A1 Lin, Song-Nan A1 Toyokawa, Tatsuya A1 Okada, Hiroyuki A1 Shiratori, Yasushi A1 Oguma, KeijiYR 2004 T1 Helicobacter pylori heat-shock protein 60 induces inflammatory responses through the Toll-like receptor-triggered pathway in cultured human gastric epithelial cells JF Microbiology, VO 150 IS 12 SP 3913 OP 3922 DO https://doi.org/10.1099/mic.0.27527-0 PB Microbiology Society, SN 1465-2080, AB Contact between Helicobacter pylori and gastric epithelial cells results in activation of NF-κB followed by secretion of interleukin (IL)-8. However, host-cell receptor(s) and their ligands involved in H. pylori-related IL-8 production have yet to be fully defined. In this study, the interaction between Toll-like receptors (TLRs), which are host receptors for pathogens involved in the innate immune response, and heat-shock protein (HSP) 60, an immune-potent antigen of H. pylori, was examined during H. pylori-induced IL-8 secretion in vitro. Recombinant H. pylori HSP60 (rHpHSP60) was prepared and added to cultured KATO III human gastric epithelial cells with or without pre-incubation with mouse monoclonal anti-TLR2 or anti-TLR4 antibodies. IL-8 mRNA expression and IL-8 protein release were analysed by Northern blotting and immunoassay. Involvement of NF-κB activation was analysed immunocytochemically by anti-NF-κB p65 antibody and ammonium pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF-κB-mediated transcriptional activation. rHpHSP60 induced IL-8 mRNA expression and IL-8 secretion in a dose-dependent manner in KATO III cells. Anti-TLR2 antibody inhibited rHpHSP60-induced IL-8 secretion by 75 %, and anti-TLR4 antibody inhibited it by 30 %. rHpHSP60 induced nuclear translocation of NF-κB p65, which was inhibited by pretreatment with anti-TLR2 antibody. Treatment with PDTC significantly decreased the secretion of IL-8 induced by rHpHSP60. These findings suggest that H. pylori HSP60 activates NF-κB and induces IL-8 production through TLR-triggered pathways in gastric epithelial cells. Thus, it is possible that H. pylori HSP60 and TLR interaction in host cells contributes to the development of gastric inflammation caused by H. pylori infection., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.27527-0