HSPA12B regulates SSeCKS-mediated astrocyte inflammatory activation in neuroinflammation
HSPA12B regulates SSeCKS-mediated astrocyte inflammatory activation in neuroinflammation
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HSPA12B 调节 SSeCKS 介导的星形胶质细胞炎症激活
DOI：
10.1016/j.yexcr.2015.09.020
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发表时间：
2015-12-10
影响因子：
3.7
通讯作者：
Lu, Xiang
中科院分区：
文献类型：
--
作者：
Li, Xiao-Hong;Huang, Jie;Lu, Xiang
反应性星形胶质细胞增生在神经炎性疾病中被认为是有益或有害的。HSPA 12 B是热休克蛋白70家族中的新成员，具有调节炎症反应的功能，也与星形胶质细胞活化有关。最近，有报道利用酵母双杂交系统在热休克蛋白A12 B（HSPA 12 B）相互作用蛋白中检测到Src抑制的C激酶底物（SSeCKS）。SSeCKS是一种主要的脂多糖（LPS）反应蛋白，在CNS炎症中通过产生促炎因子参与调节星形胶质细胞活化。在本研究中，我们发现HSPA 12 B可能调节SSeCKS的表达和活性，从而促进LPS处理的脊髓原代星形胶质细胞培养物中星形胶质细胞的炎性激活和炎性介质如TNF-α和IL-1 β的释放。HSPA 1/2B和SSeCKS相互作用促进LPS诱导的星形胶质细胞活化的机制是通过激活JNK和p38信号通路而不是ERK 1/2 MAPK信号通路。HSPA 12 B通过其两个N末端（由氨基酸1-330组成）和C末端（由氨基酸1278-1596组成）与SSeCKS结合。并且，在体内，我们证实了星形胶质细胞活化的FISPA 12 B和SSeCKS在EAE发病机制中的相互作用。HSPA 12 B-SSeCKS相互作用的调控机制可能是神经炎性疾病治疗的关键策略。(C)2015 Elsevier Inc. All rights reserved.
Reactive astrocytosis has been considered either beneficial or detrimental effection in neuroinflammatory disease. HSPA12B, a new member belongs to the 70-kDa family of heat shock proteins (HSP70) which could modulate inflammatory response, also shows an connection with the astrocyte activation. Recently, it was reported that Src-Suppressed-C Kinase Substrate (SSeCKS) was detected in heat shock protein A12B (HSPAl2B) interacting proteins using a yeast 2-hybrid system. SSeCKS, a major Lipopolysaccharide (LPS) response protein, has been involved in regulating astrocyte activation via production of proinflammatory factor in CNS inflammation. In this study, we found HSPAl2B might regulate the expression and activity of SSeCKS to promote astrocyte inflammatory activation and release of inflammatory mediators, such as TNF-alpha and IL-1 beta in spinal cord primary astroglial cultures exposed to LPS treatment. The promoting mechanism of interaction between HSPAl2B and SSeCKS on LPS-induced astrocyte activation was mediated via the activation of JNK and p38 signaling pathways but not ERK1/2 MAPK signaling pathway. HSPAl2B binded to SSeCKS via its both N terminus consisted of amino acids 1-330 and C terminus consisted of amino acids 1278-1596. And, in vivo, we confirmed the interaction between FISPAl2B and SSeCKS of astrocyte activation in the pathogenesis of EAE. The regulatory mechanisms of HSPA12B-SSeCKS interaction may possibly be the key therapeutic strategy of neuroinflammatory disease. (C) 2015 Elsevier Inc. All rights reserved.