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J Med Microbiol 56 (2007), 154-164; DOI: 10.1099/jmm.0.46882-0
© 2007 Society for General Microbiology
ISSN 1473-5644

Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes

Ying Zhao, Kenji Yokota, Kiyoshi Ayada, Yumiko Yamamoto, Tomayuki Okada, Lianhua Shen and Keiji Oguma

Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Health Science, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

Correspondence
Kenji Yokota
yokochan{at}md.okayama-u.ac.jp

Received 10 August 2006
Accepted 3 October 2006

Previous reports have indicated that Helicobacter pylori heat-shock protein 60 (H. pylori-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which H. pylori-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which H. pylori-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact H. pylori, heat-killed H. pylori and H. pylori recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-{kappa}B (NF-{kappa}B)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-{kappa}B activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in H. pylori-HSP60-induced IL-8 secretion.

Abbreviations: ERK, extracellular signal-regulated kinase; GST, glutathione S-transferase; H. pylori-HSP60, Helicobacter pylori heat-shock protein 60; HSP, heat-shock protein; IL, interleukin; JNK, c-Jun N-terminal kinase; LBP, LPS-binding protein; MAPK, mitogen-activated protein kinase; NF-{kappa}B, nuclear factor-{kappa}B; rHpHSP60, recombinant H. pylori HSP60; siRNA, small interfering RNA; TLR, Toll-like receptor.




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