Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages
Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages
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DOI：
10.1172/jci5310
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发表时间：
1999-02-01
影响因子：
15.9
通讯作者：
Libby, P
中科院分区：
文献类型：
--
作者：
Kol, A;Bourcier, T;Libby, P
衣原体和人类热休克蛋白60S(HSP60)在人类动脉粥样硬化中共存，可能在动脉粥样硬化形成过程中促进炎症。我们验证了衣原体或人热休克蛋白60激活人内皮细胞(ECs)、平滑肌细胞(SMCs)和单核细胞来源的巨噬细胞的假设。检测内皮-白细胞黏附分子-1(E-选择素)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)的表达，以及促炎细胞因子IL-6的产生。我们还检测了任一种HSP60是否诱导核因子-kappaB(NF-kappa B)，核因子-kappa B有助于这些分子的基因表达。衣原体或人热休克蛋白60均可诱导内皮细胞表达E-选择素、ICAM-1和VCAM-1，其表达水平与大肠杆菌脂多糖(LPS)诱导的水平相似。每个HSP60还显著诱导内皮细胞、SMC和巨噬细胞产生IL-6，其诱导程度与酶联免疫吸附试验(EL ISA)检测结果相似。在内皮细胞中，HSP60或HSP60均可激活含有p65和p50rel蛋白的核因子-kappaB复合体。热处理消除了所有这些影响，但没有改变关闭的能力。ColiLPS诱导这些功能。因此，衣原体和人类热休克蛋白60S激活了与动脉粥样硬化和皮损并发症相关的血管细胞功能。这些发现有助于阐明慢性无症状衣原体感染可能有助于动脉粥样硬化的病理生理机制。
Both chlamydial and human heat shock protein 60s (HSP 60), which colocalize in human atheroma, may contribute to inflammation during atherogenesis. We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). We also tested whether either HSP 60 induces nuclear factor-kappa B (NF-kappa B), which contributes to the gene expression of these molecules. Either chlamydial or human HSP 60 induced E-selectin, ICAM-1, and VCAM-1 expression on ECs similar to levels induced by Escherichia coli lipopolysaccharide (LPS). Each HSP 60 also significantly induced IL-6 production by ECs, SMCs, and macrophages to an extent similar to that induced by E. coli LPS, as assessed by enzyme-linked immunosorbent assay (ELISA). In ECs, either HSP 60 triggered activation of NF-kappa B complexes containing p65 and p50 Rel proteins. Heat treatment abolished all these effects, but did not alter the ability off. coli LPS to induce these functions. Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. These findings help to elucidate the mechanisms by which a chronic asymptomatic chlamydial infection might contribute to the pathophysiology of atheroma.