Chemokine upregulation follows cytokine expression in chronic relapsing experimental autoimmune encephalomyelitis
Chemokine upregulation follows cytokine expression in chronic relapsing experimental autoimmune encephalomyelitis
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DOI：
10.1046/j.1365-3083.2003.01285.x
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发表时间：
2003-07-01
影响因子：
3.7
通讯作者：
Ransohoff, RM
中科院分区：
文献类型：
--
作者：
Glabinski, AR;Bielecki, B;Ransohoff, RM
慢性复发性实验性自身免疫性脑脊髓炎（ChREAE）是由中枢神经系统（CNS）髓鞘成分诱导的CNS自身免疫性疾病。在早期活动期，ChREAE和多发性硬化（MS）的特征在于存在CNS中散布的血管周围炎性袖口。越来越多的证据表明，趋化因子（趋化因子）在这一过程中发挥重要作用。本研究的主要目的是分析在自身免疫性炎症过程中CNS中趋化因子表达受促炎细胞因子调节的假设。为了解决这个问题，我们分析了ChREAE过程中趋化因子和细胞因子表达之间的时间关系。趋化因子T细胞活化基因3（TCA-3）/CCL 1、单核细胞趋化蛋白-1（MCP-1）/CCL 2、巨噬细胞炎性蛋白-1 α基因表达的阶段性上调（MIP-1 α）/CCL 3、MIP-1 β/CCL 4、调节活化正常T细胞表达和分泌的（RANTES）/CCL 5和MIP-2/CXCL 2 -3以及细胞因子转化坏死因子-α在ChREAE发作期间观察到CNS中的TNF-α、β、LT-β、干扰素-γ（IFN-γ）和转化生长因子-β 1（TGF-β 1）。细胞因子TNF-β和LT-β的表达先于趋化因子上调，TGF-β 1的表达随后上调。我们的研究结果表明，在中枢神经系统自身免疫性炎症趋化因子的表达可能受到一些促炎细胞因子。
Chronic relapsing experimental autoimmune encephalomyelitis (ChREAE) is an autoimmune disease of the central nervous system (CNS) induced by CNS myelin components. In the early active stage, both ChREAE and multiple sclerosis (MS) are characterized by the presence of perivascular inflammatory cuffs disseminated in the CNS. There is growing evidence that chemoattractant cytokines (chemokines) play an important role in this process. The main goal of the present study was to analyse the hypothesis that chemokine expression in the CNS during autoimmune inflammation is regulated by proinflammatory cytokines. To address this concept, we analysed temporal relations between chemokine and cytokine expression during ChREAE. Phasic upregulation of gene expression for chemokines T-cell activation gene 3 (TCA-3)/CCL1, monocyte chemoattractant protein-1 (MCP-1)/CCL2, macrophage inflammatory protein-1 alpha (MIP-1alpha)/CCL3, MIP-1beta/CCL4, regulated on activation normal T cell expressed and secreted (RANTES)/CCL5 and MIP-2/CXCL2-3 as well as cytokines turnout necrosis factor-alpha (TNF-alpha), -beta, LT-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) in the CNS was observed during attacks of ChREAE. Expression of cytokines TNF-beta and LT-beta preceded, and the expression of TGF-beta1 followed chemokine upregulation. Our results suggest that chemokine expression during CNS autoimmune inflammation may be regulated by some proinflammatory cytokines.