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.
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.
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DOI：
10.1099/jmm.0.46882-0
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发表时间：
2007-02
影响因子：
3
通讯作者：
Yingxin Zhao;K. Yokota;K. Ayada;Yumiko Yamamoto;Tomayuki Okada;Lianhua Shen;K. Oguma
中科院分区：
文献类型：
--
作者：
Yingxin Zhao;K. Yokota;K. Ayada;Yumiko Yamamoto;Tomayuki Okada;Lianhua Shen;K. Oguma
已有报道表明，幽门螺杆菌热休克蛋白60(H.Pylori-HSP60)作为一种免疫优势抗原，可诱导人单核细胞产生IL-8。幽门螺杆菌HSP60诱导单核细胞产生IL-8的确切机制尚未完全阐明。本研究探讨了幽门螺杆菌HSP60诱导人单核细胞分泌IL-8的下游途径。完整的幽门螺杆菌、热灭活的幽门螺杆菌和重组幽门螺杆菌热休克蛋白60(RHpHSP60)均可诱导NOMO1细胞分泌IL-8，激活丝裂原活化蛋白激酶(MAPK)、细胞外信号调节蛋白激酶(ERK)和p38，但不能激活c-jun氨基末端激酶(JNK)。特异性抑制剂PD98059和U0126(用于ERK1/2信号)和SB203580(用于p38 MAPK信号)下调rHPHSP60处理的NOMO1细胞IL-8的分泌。抗Toll样受体(TLR)2抗体或TLR2小干扰RNA(SiRNA)部分抑制了IL-8的分泌，抗TLR2抗体也抑制了ERK和p38MAPK的激活。这些反应与核因子-kappaB(NF-kappaB)介导的转录激活有关，因为U0126、SB203580和抗TLR2抗体降低了核因子-kappaB的活性。综上所述，这些结果提示，人单核细胞中与TLR2识别受体相关的ERK和p38MAPK信号通路可能是HSP60诱导IL-8分泌的重要途径。
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.