Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway
Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway
复制标题
梅毒螺旋体鞭毛蛋白通过 TLR5 信号通路从人类单核细胞中引发促炎细胞因子。
DOI：
10.1016/j.imbio.2017.01.002
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发表时间：
2017-05-01
期刊：
影响因子：
2.8
通讯作者：
Wu, Yimou
中科院分区：
文献类型：
--
作者：
Xu, Man;Xie, Yafeng;Wu, Yimou
梅毒感染引起的组织损伤可能与炎症有关。然而，梅毒螺旋体的毒力因子仍不清楚，也不是导致促炎细胞因子的产生的分子机制。鞭毛蛋白是一种典型的病原体相关分子模式（PAMP），是一种诱导炎症的有效免疫原。在本研究中，我们已经证明了用梅毒螺旋体FlaB 1、FlaB 2和FlaB 3刺激人单核细胞导致白细胞介素（IL）-6和IL-8的上调。此外，通过使用小干扰RNA沉默Toll样受体5（TLR 5）基因，发现T.苍白球鞭毛蛋白诱导IL-6和IL-8表达。类似地，用编码MyD 88（pDeNyhMyD 88）的显性阴性质粒转染也引起IL-6和IL-8的下调。我们进一步研究了丝裂原活化蛋白激酶（MAPK）和核因子κ B（NF-κ B B）信号转导对IL-6和IL-8转录和翻译的相对贡献。Western Blot和免疫荧光实验显示鞭毛蛋白介导的IL-6和IL-8表达严重依赖于ERK、p38和NF-κ B。此外，发现抑制p38激酶、ERK和NF-κ B可减弱IL-6和IL-8的产生。综上所述，我们的结果表明，T.苍白球鞭毛蛋白可通过TLR 5和MAPK/NF-κ B信号通路上调THP-1细胞IL-6和IL-8的产生，这将有助于我们对T.苍白球(C)2017 Elsevier GmbH. All rights reserved.
The tissue damage caused by syphilis infection may be associated with inflammation. However, the virulence factors of Treponema pallidum are still unclear, nor are the molecular mechanisms for leading to the productions of proinflammatory cytokines. Flagellin, a classic pathogen-associated molecular pattern (PAMP), is a potent immunogen that induces inflammation. In the present study, we have demonstrated that stimulations of human monocytes with Treponema pallidum FlaBl, FlaB2, and FlaB3 result in the up regulation of interleukin (IL)-6 and IL-8. Moreover, silencing of the Toll-like receptor 5 (TLR5) gene by using small interfering RNA was found to abrogate the T. pallidum flagellins-induced IL-6 and IL 8 expressions. Similarly, transfection with the dominant negative plasmid encoding MyD88 (pDeNyhMyD88) was also giving rise to the down regulation of IL-6 and IL-8. We further investigated the relative contributions of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappa B) signaling to transcriptions and translations of IL-6 and IL-8. Western Blot and immuno fluorescence experiments revealed that flagellins-mediated IL-6 and IL-8 expressions are heavily dependent on ERK, p38, and NF-KB. In addition, inhibitions of p38 kinase, ERK, and NF-KB were found to attenuate the productions of IL-6 and IL-8. Taken together, our results indicate that T. pallidum flagellins can upregulate IL-6 and IL-8 generations via TLR5 and MAPK/NF-kappa B signaling pathways in THP-1 cells, which will improve our understanding of the pathogenesis of T. pallidum. (C) 2017 Elsevier GmbH. All rights reserved.