Toll-like receptors 2 and 4 in ischemic stroke: outcome and therapeutic values
Toll-like receptors 2 and 4 in ischemic stroke: outcome and therapeutic values
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DOI：
10.1038/jcbfm.2010.231
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发表时间：
2011-06-01
影响因子：
6.3
通讯作者：
Castillo, Jose
中科院分区：
文献类型：
--
作者：
Brea, David;Blanco, Miguel;Castillo, Jose
中风会引发强烈的炎症反应，这可能是Toll样受体(TLRs)激活的结果。然而，TLR在卒中的临床意义和治疗可能性尚不完全清楚。本研究分析TLR2、TLR4、炎症分子及内源性配体的表达与缺血性卒中患者临床转归的关系，探讨TLR2/TLR4及其内源性配体作为治疗靶点的可能性。为此，我们纳入了110名缺血性卒中患者，发现TLR2和TLR4独立地与不良预后相关，并与较高的血清白介素1β、IL6、肿瘤坏死因子a和VCAM1水平相关，TLR4与病变体积独立相关。此外，我们还开发了一种体外模型，以测试封闭TLR2/TLR4或其内源性配体的潜在治疗价值。用缺血性卒中患者血清处理培养的细胞(单核细胞和人脐静脉内皮细胞)，显示出强烈的炎症反应，当TLR2/4或细胞纤维连接蛋白(CFN)或HSP60被阻断时，这种炎症反应被阻断。结论：TLR2和TLR4与卒中患者的预后相关，TLR2/4或其内源性配体，CFN/HSP60可能成为治疗缺血性卒中的新靶点。《脑血流与代谢杂志》(2011年)31期，1424年至1431年；doi：10.1038/jcbfm.2010.231；2011年1月5日在线出版
Stroke triggers an intense inflammatory response that could be a consequence of Toll-like receptors (TLRs) activation. However, the clinical significance and the therapeutic possibilities of TLR in stroke is not completely clear. In this study, we analyze the association between the expression of TLR2 and TLR4, inflammatory molecules and endogenous ligands, and clinical outcome of ischemic stroke patients, and we test the potential of TLR2/TLR4 and their endogenous ligands as therapeutic targets. For this purpose, we included 110 patients with ischemic stroke finding that TLR2 and TLR4 are independently associated to poor outcome and correlated with higher serum levels of interleukin (IL) 1 beta, IL6, tumor necrosis factor a, and VCAM1, and that TLR4 was independently associated to lesion volume. In addition, we have developed an in vitro model to test the potential therapeutic value of blocking TLR2/TLR4 or their endogenous ligands. Cultured cells (monocytes and human umbilical vein endothelial cells) were treated with serum from ischemic stroke patients, showing a strong inflammatory response that was blocked when TLR2/4 or cellular fibronectin (cFN) or HSP60 were blocked. In conclusion, TLR2 and TLR4 are associated to outcome in stroke patients and TLR2/4 or their endogenous ligands, cFN/HSP60 could be new therapeutic targets for ischemic stroke. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1424-1431; doi:10.1038/jcbfm.2010.231; published online 5 January 2011