Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway.
Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway.
复制标题
梅毒螺旋体鞭毛蛋白 FlaA2 通过 Toll 样受体 2 信号通路诱导 THP-1 细胞分泌 IL-6
DOI：
10.1016/j.molimm.2016.11.005
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发表时间：
2017
影响因子：
3.6
通讯作者：
Wu Yimou
中科院分区：
文献类型：
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作者：
Xie Yafeng;Xu Man;Xiao Yongjian;Liu Zhuoran;Jiang Chuanhao;Kuang Xingxing;Wang Chuan;Wu Haiying;Peng Jing;Li Chun;Wang Yu;Liu Huaming;Liu Bin;Zhang Xiaotuan;Zhao Feijun;Zeng Tiebing;Liu Shuangquan;Wu Yimou
梅毒螺旋体膜蛋白被认为是炎症发生和发展的有效诱导物。本研究探讨了T. pallidumflagellin FlaA2。鞭毛蛋白FlaA 2可诱导人单核细胞表达IL-6，增加ERK、p38和NF-κB的磷酸化，但对JNK的磷酸化无影响。同样，FlaA 2诱导的IL-6产生被ERK、p38和NF-κB抑制剂减弱，但JNK抑制剂不减弱。免疫荧光分析表明，鞭毛蛋白FlaA 2可刺激IκBα从胞浆向核转位，而特异性抑制剂BAY 11 -7082可抑制这一现象。FlaA 2诱导的IL-6表达也被证实通过转染MyD 88的显性阴性（DN）质粒废除。我们进一步证明了DN-TLR 2转染足以减弱IL-6表达和ERK、p38和IκBα的磷酸化。这些结果表明，鞭毛蛋白FlaA 2通过TLR 2、MyD 88、ERK、p38和NF-κB等信号通路诱导单核细胞产生IL-6，可能参与了T.苍白球
Treponema pallidumsubsp.pallidummembrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated withT. pallidumflagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be attenuated by inhibitors for ERK, p38, and NF-κB, but not by JNK inhibitor. Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the translocation of IκBα from the cytosol to the nucleus, and this phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2–induced IL-6 expression was also proved to be abrogated by transfection with dominant negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN-TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK, p38, and IκBα. These results suggest that flagellin FlaA2 induces IL-6 production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-κB in monocytes, which could contribute to the pathogenesis ofT. pallidum.