NITRIC-OXIDE DECREASES CYTOKINE-INDUCED ENDOTHELIAL ACTIVATION - NITRIC-OXIDE SELECTIVELY REDUCES ENDOTHELIAL EXPRESSION OF ADHESION MOLECULES AND PROINFLAMMATORY CYTOKINES
NITRIC-OXIDE DECREASES CYTOKINE-INDUCED ENDOTHELIAL ACTIVATION - NITRIC-OXIDE SELECTIVELY REDUCES ENDOTHELIAL EXPRESSION OF ADHESION MOLECULES AND PROINFLAMMATORY CYTOKINES
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DOI：
10.1172/jci118074
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发表时间：
1995-07-01
影响因子：
15.9
通讯作者：
LIAO, JK
中科院分区：
文献类型：
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作者：
DECATERINA, R;LIBBY, P;LIAO, JK
为了验证一氧化氮（NO）限制内皮细胞活化的假设，我们用几种NO供体处理了精氨酸刺激的人隐静脉内皮细胞，并评估了它们对血管细胞粘附分子-1（VCAM（-）1）诱导表达的影响。通过细胞表面酶免疫分析和流式细胞术测定，NO以浓度依赖性方式抑制白细胞介素（IL）-1 α刺激的VCAM-1表达35-55%。在非静态试验中，这种抑制作用被单核细胞与内皮细胞单层的粘附减少所抵消，不受cGMP类似物的影响，并且在IL-1 α、IL-1 β、IL-4、肿瘤坏死因子（TNF α）或细菌脂多糖刺激后在数量上相似。NO还降低了内皮细胞表达的其他白细胞粘附分子（E-选择素，并在较小程度上，细胞间粘附分子-1）和分泌的细胞因子（IL-6和IL-8）。L-N-单甲基精氨酸抑制内源性NO的产生也诱导VCAM-1的表达，但不增加精氨酸诱导的VCAM-1的表达。核运行试验，转染研究，使用各种VCAM-1启动子报告基因构建体，和电泳迁移率变动分析表明，NO抑制VCAM-1基因转录，部分，通过抑制NF-κ B。我们认为，NO限制内皮细胞活化和抑制单核细胞粘附的能力可能有助于其在血管壁内的抗动脉粥样硬化和抗血栓性质。
To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM(-)1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall.