Mycoplasma bovis-derived lipid-associated membrane proteins activate IL-1β production through the NF-κB pathway via toll-like receptor 2 and MyD88
Mycoplasma bovis-derived lipid-associated membrane proteins activate IL-1β production through the NF-κB pathway via toll-like receptor 2 and MyD88
复制标题
牛支原体衍生的脂质相关膜蛋白通过 Toll 样受体 2 和 MyD88 通过 NF-κB 途径激活 IL-1β 产生
DOI：
10.1016/j.dci.2015.10.017
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发表时间：
2016-02-01
影响因子：
2.9
通讯作者：
Xin, Jiuqing
中科院分区：
文献类型：
--
作者：
Wang, Yang;Liu, Suli;Xin, Jiuqing
牛支原体可引起小牛肺炎、中耳炎和关节炎，给全世界养牛业造成经济损失。M.牛的发病机制部分是由于过度的免疫应答。脂质相关膜蛋白（Lipid-associated membrane proteins，LAMPs）能有效诱导宿主天然免疫。然而，M.牛源性LAMP和Toll样受体（Tilts），或引发活性炎症和NF-κ B活化的信号传导途径还不完全清楚。在这里，我们发现，IL-1 β的表达诱导胚胎牛肺（EBL）细胞刺激M。牛来源的LAMP。亚细胞定位分析显示，细胞核p65易位后，EBL细胞与M。牛来源的LAMP。NF-κ B B抑制剂逆转M.牛来源的LAMP诱导的IL-1 β表达。TLR 2和髓样分化初级反应基因88（MyD 88）过表达增加LAMP依赖性IL-1 β诱导。TLR 2中和抗体在LAMP刺激期间减少IL-1 β表达。在显性负性MyD 88蛋白过表达后，LAMP也抑制IL-1 β表达。这些结果表明M.牛来源的LAMP通过TLR 2和MyD 88经由NF-κ B途径激活IL-1 β产生。(C)2015爱思唯尔有限公司版权所有。
Mycoplasma bovis causes pneumonia, otitis media, and arthritis in young calves, resulting in economic losses to the cattle industry worldwide. M. bovis pathogenesis results in part from excessive immune responses. Lipid-associated membrane proteins (LAMPs) can potently induce host innate immunity. However, interactions between M. bovis-derived LAMPs and Toll-like receptors (Tilts), or signaling pathways eliciting active inflammation and NF-kappa B activation, are incompletely understood. Here, we found that IL-1 beta expression was induced in embryonic bovine lung (EBL) cells stimulated with M. bovis-derived LAMPs. Subcellular-localization analysis revealed nuclear p65 translocation following EBL cell stimulation with M. bovis-derived LAMPs. An NF-kappa B inhibitor reversed M. bovis-derived LAMP-induced IL-1 beta expression. TLR2 and myeloid differentiation primary response gene 88 (MyD88) overexpression increased LAMP-dependent IL-1 beta induction. TLR2-neutralizing antibodies reduced IL-1 beta expression during LAMP stimulation. LAMPs also inhibited IL-1 beta expression following overexpression of a dominant-negative MyD88 protein. These results suggested that M. bovis-derived LAMPs activate IL-1 beta production through the NF-kappa B pathway via TLR2 and MyD88. (C) 2015 Elsevier Ltd. All rights reserved.