Inhibition of microglial CD40 expression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10
Inhibition of microglial CD40 expression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10
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DOI：
10.1016/s0165-5728(02)00059-0
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发表时间：
2002-05-01
影响因子：
3.3
通讯作者：
Jonakait, GM
中科院分区：
文献类型：
--
作者：
Kim, WK;Ganea, D;Jonakait, GM
小胶质细胞是中枢神经系统(CNS)免疫反应的内源性介质。激活的小胶质细胞表达共刺激分子CD40和B7，这两个分子对T细胞的激活和小胶质细胞的进一步激活同样重要。本研究旨在探讨抗炎神经肽--垂体腺苷酸环化酶激活多肽(PACAP)和血管活性肠肽(VIP)对小胶质细胞和BV2细胞共刺激分子表达的调节作用。神经肽可抑制活化的小胶质细胞CD40和B7-2mRNA的表达。PACAP可降低活化的小胶质细胞表面CD40和B7-2的表达。加入抗IL-10抗体可完全阻断PACAP对内毒素(LPS)诱导的CD40表达的抑制，表明PACAP抑制至少部分是由IL-10介导的。事实上，PACAP提高了脂多糖诱导的小胶质细胞中IL-10mRNA和蛋白的水平。这些数据表明，PACAP通过增加IL-10蛋白，下调小胶质细胞上重要的共刺激分子的表达，从而可能影响CNS免疫。(C)2002 Elsevier Science B.V.保留所有权利。
Microglia are intrinsic mediators of the central nervous system (CNS) immune response induced by a variety of insults. Activated microglia express costimulatory molecules CD40 and B7 that are important equally for T-cell activation and further activation of microglia. In this study, we sought to investigate the regulation of costimulatory molecule expression on primary microglia and microglial cell line, BV2, by pituitary adenylyl cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), potent anti-inflammatory neuropeptides. The neuropeptides inhibited CD40 and B7-2 mRNA expression in activated microglia. PACAP decreased surface expression of CD40 and B7-2 on activated microglia. The inclusion of an anti-IL-10 antibody completely abrogated PACAP inhibition of lipopolysaccharide (LPS)-induced CD40 expression, suggesting that PACAP inhibition is at least in part mediated by IL-10. Indeed, PACAP enhanced LPS-induced IL-10 mRNA and protein levels in microglia. These data indicate that PACAP, through an increase in IL-10 protein, can down-regulate important costimulatory molecule expression on microglia, thereby possibly affecting CNS immunity. (C) 2002 Elsevier Science B.V. All rights reserved.