AIM:To examine the effect of sanggenon C on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC),and explore its mechanism.METHODS:Adhesion of PMN to HSC was measured by MTF colorimetry.Cell-ELISA and RT-PCR methods were used to examine the expression of adhesion molecules ICAM-I and VCAM-1.Activation of nuclear factor-kappa B (NF-κB) was measured by electrophoretic mobility shift assays ( EMSA ) method.RESULTS:Sanggenon C effectively inhibited TNF-α (50 kU@L-1 for 12 h) and IL-lβ (50 kU@L-1 for 12 h) induced adhesion of PMN to HSC ( IC50 27.29 nmol@ L- 1 and 54.45 nmol@L- 1,respectively) in a concentration-dependent manner.Adhesion molecule VCAM-1 surface protein and mRNA expression induced by TNF-α 50 kU@ L-1 were significantly inhibited by sanggenon C,nevertheless,for ICAM-1 only surface protein expression being inhibited.The activation of NF-κB was also extensively inhibited by sanggenon C.CONCLUSION:Sanggenon C inhibitedTNF-α-stimulated PMN-HSC adhesion and expression of VCAM-1 by suppressing the activation of NF-κB.%目的:观察化合物Sanggenon C对人外周血多形核白细胞(PMN)与人滑膜细胞(HSC)粘附的抑制作用,并探讨其作用机制.方法:MTT比色法研究PMN与HSC粘附,Cell-ELISA及RT-PCR法研究HSC粘附分子ICAM-1和VCAM-1表达,EMSA研究核转录因子NF-κB的活化.结果:Sanggenon C在0.01-10μmol@L-1范围内均可显著抑制TNF-α50kU@L-1与IL-1β诱导的HSC与PMN粘附,其IC50分别为27.29nmol@L-1和54.45 nmol@L-1;Sanggenon C可显著抑制HSC表面ICAM-1和VCAM-1蛋白表达,同时也显著抑制VCAM-1 mRNA表达,但对ICAM-1 mRNA表达无显著影响;Sanggenon C在l-10 μmol@L-1浓度下也可显著抑制TNF-α对NF-κB的活化.结论:Sanggenon C是一个有效的人PMN与HSC粘附抑制剂,其作用机制可能是通过抑制NF-κB的活化,进而抑制HSC表面VCAM-1的表达或抑制ICAM-1转录后调控过程而实现的.
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