Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators
Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators
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DOI：
10.1002/glia.20328
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发表时间：
2006-05-01
期刊：
影响因子：
6.2
通讯作者：
Van Noort, JM
中科院分区：
文献类型：
--
作者：
Bsibsi, M;Persoon-Deen, C;Van Noort, JM
Toll样受体（TLR）是在包括CNS神经胶质细胞在内的多种细胞类型上表达的先天免疫受体。一般而言，TLR与特定微生物配体组的结合触发促炎因子的产生并增强抗原呈递细胞功能。然而，TLR在CNS中的功能作用仍然知之甚少。虽然培养的成人星形胶质细胞主要表达TLR 4，但当被促炎细胞因子、TLR 3或TLR 4激动剂或氧化应激激活时，它们显示出对TLR 3的显著强的和选择性的诱导。对星形胶质细胞对TLR 3或TLR 4激活的反应的基因分析显示，TLR 3而不是TLR 4诱导一系列神经保护介质和调节细胞生长、分化和迁移的几种其他分子的表达。此外，TLR 3触发抗炎细胞因子（包括白细胞介素-9（IL-9）、IL-10和IL-11）的产生增强以及IL-12和IL-23的p40亚基的下调。在功能测定中发现集体TLR 3诱导的产物抑制星形胶质细胞生长，促进人内皮细胞生长，并且重要的是，增强器官型人脑切片培养物中的神经元存活。总之，我们的数据表明，TLR 3在炎症时在人类星形胶质细胞上被诱导，并且当被激活时，介导全面的神经保护反应，而不是极化的促炎反应。(c)2006 Wiley-Liss，Inc.
Toll-like receptors (TLRs) are innate immunity receptors that are expressed on a wide range of cell types, including CNS glial cells. In general, TLR engagement by specific sets of microbial ligands triggers production of pro-inflammatory factors and enhances antigen-presenting cell functions. The functional roles of TLR in the CNS, however, are still poorly understood. While adult human astrocytes in culture dominantly express TLR4, they display a strikingly strong and selective induction of TLR3 when activated by pro-inflammatory cytokines, TLR3 or TLR4 agonists, or oxidative stress. Gene profiling analysis of the astrocyte response to either TLR3 or TLR4 activation revealed that TLR3, but not TLR4, induces expression of a range of neuroprotective mediators and several other molecules that regulate cellular growth, differentiation, and migration. Also, TLR3 triggered enhanced production of anti-inflammatory cytokines including interleukin-9 (IL-9), IL-10, and IL-11 and downregulation of the p40 subunit of IL-12 and IL-23. The collective TLR3-induced products were found in functional assays to inhibit astrocyte growth, promote human endothelial cell growth, and importantly, to enhance neuronal survival in organotypic human brain slice cultures. Together, our data indicate that TLR3 is induced on human astrocytes upon inflammation and when activated, mediates a comprehensive neuroprotective response rather than a polarized pro-inflammatory reaction. (c) 2006 Wiley-Liss, Inc.