Recombinant Mtb9.8 of Mycobacterium bovis stimulates TNF-alpha and IL-1 beta secretion by RAW264.7 macrophages through activation of NF-kappa B pathway via TLR2

文献类型： 外文期刊

第一作者： Liu, Shuqing

作者： Liu, Shuqing;Zhu, Wuyang;Liu, Shuqing;Jia, Hong;Hou, Shaohua;Xin, Ting;Guo, Xiaoyu;Zhang, Gaimei;Gao, Xintao;Li, Ming;Zhu, Hongfei

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2018 年 8 卷

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收录情况： SCI

摘要： The Mtb9.8 antigenic protein of Mycobacterium bovis/Mycobacterium tuberculosis has been identified as a target of the T-cell response. However, the interaction of Mtb9.8 with Toll-like receptors (TLRs) and the relevant signaling pathways have not been fully clarified. In this study, recombinant Mtb9.8 (rMtb9.8) derived from M. bovis-stimulated RAW264.7 cells initiated the secretion of TNF-alpha and IL-1 beta in a dose-dependent manner. Blocking assays show that TLR2-neutralizing antibody decreases the production of TNF-alpha and IL-1 beta. Moreover, NF-kappa B activation is associated with TNF-alpha and IL-1 beta production by rMtb9.8 stimulation, and rMtb9.8 stimulation also induces the phosphorylation of NF-kappa B p65 at Ser536 and its rapid nuclear translocation in RAW264.7 cells. Furthermore, NF-kappa B luciferase activity is rapidly activated in response to rMtb9.8 in RAW264.7 cells and is also significantly increased in rMtb9.8-induced HEK293-TLR2. However, these activations were abrogated in cells with a dominantnegative mutation of NF-kappa B p65 and by treatment with anti-TLR2 antibody. We also find that rMtb9.8 induces the activation of IRF-1. These findings indicate that M. bovis-derived rMtb9.8 activates the NF-kappa B pathway via TLR2 in RAW264.7 cells. In particular, it phosphorylates NF-kappa B p65 at Ser536 and induces nuclear translocation, thereby leading to the production of TNF-alpha and IL-1 beta, which correlates with the induction of IRF-1.

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