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IBUPROFEN INHIBITS PYROGEN-DEPENDENT EXPRESSION OF VCAM-1 AND ICAM-1 ON HUMAN ENDOTHELIAL CELLS

机译:布洛芬抑制人内皮细胞上VCAM-1和ICAM-1的热原依赖性表达

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摘要

Leukocyte adhesion and transmigration through the endothelial cell (EC) layer plays a crucial role in inflammation. IL-1 alpha and TNF alpha increase EC-adhesiveness for leukocytes by stimulating surface expression of ICAM-1 (intercellular adhesion molecule 1, CD54), VCAM-1 (vascular cell adhesion molecule 1, CD106) and E-selectin (CD62E). In this study, the effects of ibuprofen on IL-1 alpha and TNF alpha-induced expression of ICAM-1, VCAM-1 and E-selectin on cultured human umbilical vein EC (HUVEC) were analyzed. Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. Ibuprofen was identified as a potent inhibitor of IL-1 alpha and TNF alpha-induced surface expression of VCAM-1 and a less potent inhibitor of pyrogen-induced expression of ICAM-1, whereas no effect on E-selectin was found. The effects of ibuprofen on VCAM-1 expression were dose-dependent (IC50 [IL-1 alpha]: 0.5 mM; IC50 [TNF alpha]: 0.5 mM) and time-dependent with maximum responses observed after 18 h. Moreover, ibuprofen abrogated pyrogen-dependent adhesion of leukocytes to HUVEC. Ibuprofen also inhibited VCAM-1 mRNA expression in pyrogen activated EC. VCAM-1-downregulation on EC by ibuprofen may contribute to the anti-inflammatory actions of the drug. [References: 58]
机译:白细胞粘附和通过内皮细胞(EC)层的迁移在炎症中起关键作用。 IL-1α和TNFα通过刺激ICAM-1(细胞间粘附分子1,CD54),VCAM-1(血管细胞粘附分子1,CD106)和E-选择素(CD62E)的表面表达来提高白细胞的EC粘附性。在这项研究中,分析了布洛芬对培养的人脐静脉EC(HUVEC)上IL-1α和TNFα诱导的ICAM-1,VCAM-1和E-选择素表达的影响。暴露于IL-1α或TNFα导致VCAM-1,ICAM-1和E-选择素的表达增加。布洛芬被鉴定为IL-1α和TNFα诱导的VCAM-1表面表达的有效抑制剂,而热原诱导的ICAM-1表达的效力较弱,而未发现对E-选择蛋白的影响。布洛芬对VCAM-1表达的影响是剂量依赖性的(IC50 [IL-1α]:0.5 mM; IC50 [TNFα]:0.5 mM),并且是时间依赖性的,在18小时后观察到最大反应。此外,布洛芬消除了白细胞对HUVEC的热原依赖性粘附。布洛芬还抑制热原激活的EC中的VCAM-1 mRNA表达。布洛芬对EC的VCAM-1下调可能有助于药物的抗炎作用。 [参考:58]

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