Cigarette Smoke Amplifies Inflammatory Response and Atherosclerosis Progression Through Activation of the H1R-TLR2/4-COX2 Axis.
Cigarette Smoke Amplifies Inflammatory Response and Atherosclerosis Progression Through Activation of the H1R-TLR2/4-COX2 Axis.
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DOI：
10.3389/fimmu.2015.00572
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发表时间：
2015
影响因子：
7.3
通讯作者：
Dileepan KN
中科院分区：
文献类型：
--
作者：
Barua RS;Sharma M;Dileepan KN
新出现的证据表明，感染和持续性炎症是动脉粥样硬化性心血管疾病（CVD）发病机制的关键因素。虽然香烟烟雾（CS）促进动脉粥样硬化性CVD是公认的，但关于CS和间歇性或慢性亚临床感染对动脉粥样硬化的集体影响的潜在影响知之甚少。我们以前的研究表明，肥大细胞衍生的组胺和脂多糖（LPS）协同增强内皮细胞的炎症反应。我们进一步注意到组胺和LPS之间的协同作用是由于组胺受体和Toll样受体4（TLR 4）表达和功能的相互上调。这些结果表明，肥大细胞介质和细菌制剂对血管系统的联合和持续作用是CVD的危险因素。我们最近的数据表明，CS提取物增强组胺和LPS诱导的环氧合酶-2（考克斯-2）在内皮细胞中的表达，表明CS和肥大细胞介质可能共同放大血管壁中的炎症反应。我们假设CS增强组胺介导的TLR 2/TLR 4信号在内皮细胞中的上调，并促进动脉粥样硬化的进展。本文就CS和尼古丁对“组胺-TLR-考克斯-2轴”的调节作用提出了我们的观点。
Emerging evidence suggests that infection and persistent inflammation are key players in the pathogenesis of atherosclerotic cardiovascular disease (CVD). Although it is well established that cigarette smoke (CS) promotes atherosclerotic CVD, very little is known about the potential impact of the collective effects of CS and intermittent or chronic subclinical infection on atherosclerosis. Our previous studies demonstrated that mast cell-derived histamine and lipopolysaccharide (LPS) synergistically enhance endothelial cell inflammatory response. We further noted that the synergy between histamine and LPS was due to reciprocal upregulation of histamine receptor and Toll-like receptor 4 (TLR4) expression and functions. These results suggest that the combined and persistent effects of mast cell mediators and bacterial agents on the vasculature are risk factors of CVD. Our recent data demonstrated that CS extract enhances histamine- and LPS-induced expression of cyclooxygenase-2 (COX-2) in endothelial cells, suggesting that CS and mast cell mediators may collectively amplify inflammatory response in the vessel wall. We hypothesize that CS enhances histamine-mediated upregulation of TLR2/TLR4 signaling in the endothelium and promotes progression of atherosclerosis. This article presents our perspective on the modulatory effects of CS and nicotine on the “histamine-TLR-COX-2 axis.”