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.
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-kappaB (NF-kappaB)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-kappaB 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.
Zhao
Ying
Y
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.
Yokota
Kenji
K
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.
Ayada
Kiyoshi
K
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.
Yamamoto
Yumiko
Y
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.
Okada
Tomayuki
T
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.
Shen
Lianhua
L
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.
Oguma
Keiji
K
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.
D001426:Bacterial Proteins / Q000276:immunology*; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology*; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
D001426:Bacterial Proteins; D002070:Butadienes; D018834:Chaperonin 60; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016209:Interleukin-8; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051195:Toll-Like Receptor 2; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one