Involvement of the antimicrobial peptide LL-37 in human atherosclerosis
Involvement of the antimicrobial peptide LL-37 in human atherosclerosis
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DOI：
10.1161/01.atv.0000223901.08459.57
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发表时间：
2006-07-01
影响因子：
8.7
通讯作者：
Yan, Zhong-qun
中科院分区：
文献类型：
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作者：
Edfeldt, Kristina;Agerberth, Birgitta;Yan, Zhong-qun
目的-抗菌肽是天然免疫系统的效应分子。要了解动脉粥样硬化血管先天免疫的功能，我们调查的作用LL-37，cathelicidin抗菌肽，在疾病process.Methods和Results -使用实时聚合酶链反应，我们发现了6倍的人阳离子抗菌蛋白18/LL-37在人类动脉粥样硬化病变的转录与正常动脉相比。动脉粥样硬化斑块的免疫组化分析显示，LL-37主要由巨噬细胞和一些内皮细胞表达。Westernblot证实动脉粥样硬化标本中存在活性LL-37肽和丰富的前体蛋白。为了理解LL-37产生在动脉粥样硬化中的功能意义，在用LL-37处理的内皮细胞中评估转录谱。我们的数据表明，LL-37诱导内皮细胞中粘附分子细胞间粘附分子-1和趋化因子单核细胞趋化蛋白1的表达。有趣的是，肺炎衣原体经受住了LL-37在体外的抗菌活性，虽然炎症反应诱导infection. Conclusion-LL-37是产生于动脉粥样硬化病变，在那里它可能作为一种免疫调节剂激活粘附分子和趋化因子的表达，从而增强先天免疫动脉粥样硬化。
Objective - Antimicrobial peptides are effector molecules of the innate immune system. To understand the function of vascular innate immunity in atherosclerosis, we investigated the role of LL-37, a cathelicidin antimicrobial peptide, in the disease process.Methods and Results - Using real-time polymerase chain reaction, we found a 6-fold increase in human cationic antimicrobial protein 18/LL-37 transcript in human atherosclerotic lesions compared with normal arteries. Immunohistochemical analysis of atherosclerotic plaques showed that LL-37 was expressed mainly by macrophages and some endothelial cells. Western blot demonstrated existence of active LL-37 peptide and abundant proprotein in atheroma specimens. To understand the functional implication of LL-37 production in atherosclerosis, the transcription profile was assessed in endothelial cells treated with LL-37. Our data show that LL-37 induces expression of the adhesion molecule intercellular adhesion molecule-1 and the chemokine monocyte chemoattractant protein 1 in endothelial cells. Intriguingly, Chlamydia pneumoniae withstood the antimicrobial activity of LL-37 in vitro, although inflammatory response was induced on infection.Conclusion - LL-37 is produced in atherosclerotic lesions, where it may function as an immune modulator by activating adhesion molecule and chemokine expression, thus enhancing innate immunity in atherosclerosis.