Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall components
Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall components
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DOI：
10.1111/j.1365-2567.2004.01946.x
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发表时间：
2004-10-01
期刊：
影响因子：
6.4
通讯作者：
Dileepan, KN
中科院分区：
文献类型：
--
作者：
Talreja, J;Kabir, MH;Dileepan, KN
组胺是肥大细胞释放的一种主要炎症分子，已知可以激活内皮细胞。然而，其调节内皮细胞对细菌产物反应的能力尚未得到评价。在这项研究中，我们确定了组胺调节革兰氏阴性和革兰氏阳性细菌细胞壁成分的内皮细胞炎症反应的能力，并评估了Toll样受体（TLR）2和4在组胺和细菌病原体之间的合作中的作用。在组胺存在或不存在的情况下，将人脐静脉内皮细胞（HUVEC）与脂多糖（LPS）、脂磷壁酸（LTA）或肽聚糖（PGN）孵育，并测定白细胞介素-6（IL-6）的表达和释放以及NF-κ B易位。还评估了组胺对TLR 2和TLR 4 mRNA和蛋白表达的影响。LPS、LTA和PGN均可显著增强HUVEC IL-6 mRNA表达和IL-6分泌。单独使用组胺可显著增强HUVEC中IL-6 mRNA的表达，但不能刺激IL-6的成比例释放。当HUVEC与LPS、LTA或PGN在组胺存在下孵育时，注意到IL-6产生和mRNA表达的显著扩增。HUVEC组成型表达TLR2和TLR4 mRNA和蛋白，这些进一步增强组胺。与TLR信号相关的辅助分子MD-2和MyD88编码的mRNA的表达未受组胺处理的影响。这些结果表明，组胺上调TLR2和TLR4的表达，并放大内皮细胞对革兰氏阴性和革兰氏阳性细菌组分的炎症反应。
Histamine is a major inflammatory molecule released from the mast cell, and is known to activate endothelial cells. However, its ability to modulate endothelial responses to bacterial products has not been evaluated. In this study we determined the ability of histamine to modulate inflammatory responses of endothelial cells to Gram-negative and Gram-positive bacterial cell wall components and assessed the role of Toll-like receptors (TLR) 2 and 4 in the co-operation between histamine and bacterial pathogens. Human umbilical vein endothelial cells (HUVEC) were incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or peptidoglycan (PGN) in the presence or absence of histamine, and the expression and release of interleukin-6 (IL-6), and NF-kappaB translocation were determined. The effect of histamine on the expression of mRNA and proteins for TLR2 and TLR4 was also evaluated. Incubation of HUVEC with LPS, LTA and PGN resulted in marked enhancement of IL-6 mRNA expression and IL-6 secretion. Histamine alone markedly enhanced IL-6 mRNA expression in HUVEC, but it did not stimulate proportional IL-6 release. When HUVEC were incubated with LPS, LTA, or PGN in the presence of histamine marked amplification of both IL-6 production and mRNA expression was noted. HUVEC constitutively expressed TLR2 and TLR4 mRNA and proteins, and these were further enhanced by histamine. The expression of mRNAs encoding MD-2 and MyD88, the accessory molecules associated with TLR signalling, were unchanged by histamine treatment. These results demonstrate that histamine up-regulates the expression of TLR2 and TLR4 and amplifies endothelial cell inflammatory responses to Gram-negative and Gram-positive bacterial components.