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Toll-like receptors 2 and 4 in ischemic stroke: outcome and therapeutic values.

机译:缺血性中风中的Toll样受体2和4:结果和治疗价值。

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摘要

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)1beta, IL6, tumor necrosis factor alpha, 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.
机译:中风会触发强烈的炎症反应,这可能是Toll样受体(TLR)激活的结果。但是,TLR在中风的临床意义和治疗可能性尚不完全清楚。在这项研究中,我们分析了TLR2和TLR4的表达,炎性分子和内源性配体与缺血性中风患者的临床结局之间的关联,并测试了TLR2 / TLR4及其内源性配体作为治疗靶标的潜力。为此,我们纳入了110例缺血性卒中患者,发现TLR2和TLR4与不良预后独立相关,并与白细胞介素(IL)1beta,IL6,肿瘤坏死因子α和VCAM1的较高血清水平相关,而TLR4独立与病变体积有关。此外,我们已经开发了一种体外模型来测试阻断TLR2 / TLR4或其内源性配体的潜在治疗价值。用缺血性中风患者的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,当阻断TLR2 / 4或细胞纤连蛋白(cFN)或HSP60时,炎症反应被阻断。总之,TLR2和TLR4与卒中患者的预后相关,TLR2 / 4或它们的内源性配体cFN / HSP60可能是缺血性卒中的新治疗靶标。

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