Kapiotis S, Sengoelge G, Sperr W R, Baghestanian M, Quehenberger P, Bevec D, Li S R, Menzel E J, Mühl A, Zapolska D, Virgolini I, Valent P, Speiser W
Clin. Inst. of Med., Univ. Vienna, Austria.
Life Sci. 1996;58(23):2167-81. doi: 10.1016/0024-3205(96)00210-x.
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.
白细胞通过内皮细胞（EC）层的黏附和迁移在炎症过程中起着关键作用。白细胞介素-1α（IL-1α）和肿瘤坏死因子α（TNFα）通过刺激细胞间黏附分子-1（ICAM-1，CD54）、血管细胞黏附分子-1（VCAM-1，CD106）和E-选择素（CD62E）的表面表达来增加内皮细胞对白细胞的黏附性。在本研究中，分析了布洛芬对IL-1α和TNFα诱导的人脐静脉内皮细胞（HUVEC）上ICAM-1、VCAM-1和E-选择素表达的影响。暴露于IL-1α或TNFα会导致VCAM-1、ICAM-1和E-选择素的表达增加。布洛芬被确定为IL-1α和TNFα诱导的VCAM-1表面表达的强效抑制剂，以及热原诱导的ICAM-1表达的较弱抑制剂，而对E-选择素没有影响。布洛芬对VCAM-1表达的影响呈剂量依赖性（IC50[IL-1α]：0.5 mM；IC50[TNFα]：0.5 mM）和时间依赖性，在18小时后观察到最大反应。此外，布洛芬消除了热原依赖性白细胞与HUVEC的黏附。布洛芬还抑制了热原激活的内皮细胞中VCAM-1 mRNA的表达。布洛芬对内皮细胞上VCAM-1的下调可能有助于该药物的抗炎作用。
