Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States.
Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States.
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DOI：
10.1016/j.celrep.2018.04.110
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发表时间：
2018-05-29
期刊：
影响因子：
8.8
通讯作者：
Miller YI
中科院分区：
文献类型：
--
作者：
Woller SA;Choi SH;An EJ;Low H;Schneider DA;Ramachandran R;Kim J;Bae YS;Sviridov D;Corr M;Yaksh TL;Miller YI
载脂蛋白A-I结合蛋白（AIBP）通过增加从质膜去除过量胆固醇来减少脂筏丰度。在这里，我们报告说，AIBP预防和逆转与神经炎症介导的脊髓伤害性加工相关的过程。其机制涉及AIBP与Toll样受体-4（TLR 4）的结合以及AIBP与活化的小胶质细胞的结合增加，后者介导炎症细胞中脂筏的选择性调节。AIBP介导的脂筏减少下调LPS诱导的TLR 4二聚化，炎症信号和小胶质细胞中细胞因子的表达。在小鼠中，鞘内注射AIBP减少了脊髓髓样细胞脂筏、TLR 4二聚化、神经炎症和胶质细胞活化。鞘内AIBP逆转了小鼠中建立的异常性疼痛，其中疼痛状态由化疗顺铂、足底福尔马林或鞘内LPS诱导，所有已知的促伤害性干预均受TLR 4信号转导调节。这些发现证明了AIBP调节神经炎症的机制，并表明AIBP在治疗既存疼痛状态方面的治疗潜力。
Apolipoprotein A-I binding protein (AIBP) reduces lipid raft abundance by augmenting removal of excess of cholesterol from the plasma membrane. Here, we report that AIBP prevents and reverses processes associated with neuroinflammatory-mediated spinal nociceptive processing. The mechanism involves AIBP binding to Toll-like-receptor-4 (TLR4) and increased binding of AIBP to activated microglia, which mediates selective regulation of lipid rafts in inflammatory cells. AIBP-mediated lipid raft reductions downregulated LPS-induced TLR4 dimerization, inflammatory signaling and expression of cytokines in microglia. In mice, intrathecal injections of AIBP reduced spinal myeloid cell lipid rafts, TLR4 dimerization, neuroinflammation, and glial activation. Intrathecal AIBP reversed established allodynia in mice in which pain states were induced by the chemotherapeutic cisplatin, intraplantar formalin, or intrathecal LPS, all pro-nociceptive interventions known to be regulated by TLR4 signaling. These findings demonstrate a mechanism by which AIBP regulates neuroinflammation and suggest the therapeutic potential for AIBP in treating preexisting pain states.
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