李良成, 侯琦, 郭颖, 程桂芳. 美洛昔康抑制正常人中性粒细胞与滑膜细胞粘附的作用机理研究J. 药学学报, 2002, 37(2): 103-107.
引用本文: 李良成, 侯琦, 郭颖, 程桂芳. 美洛昔康抑制正常人中性粒细胞与滑膜细胞粘附的作用机理研究J. 药学学报, 2002, 37(2): 103-107.
LI Liang-cheng, HOU Qi, GUO Ying, CHENG Gui-fang. INHIBITORY EFFECT OF MELOXICAM ON HUMAN POLYMORPHONUCLEAR LEUKOCYTE ADHESION TO HUMAN SYNOVIAL CELLJ. Acta Pharmaceutica Sinica, 2002, 37(2): 103-107.
Citation: LI Liang-cheng, HOU Qi, GUO Ying, CHENG Gui-fang. INHIBITORY EFFECT OF MELOXICAM ON HUMAN POLYMORPHONUCLEAR LEUKOCYTE ADHESION TO HUMAN SYNOVIAL CELLJ. Acta Pharmaceutica Sinica, 2002, 37(2): 103-107.

美洛昔康抑制正常人中性粒细胞与滑膜细胞粘附的作用机理研究

INHIBITORY EFFECT OF MELOXICAM ON HUMAN POLYMORPHONUCLEAR LEUKOCYTE ADHESION TO HUMAN SYNOVIAL CELL

  • 摘要: 目的研究美洛昔康对正常人中性粒细胞(polymorphonuclear leukocyte,PMN)与滑膜细胞(human synovial cell,HSC)粘附的抑制作用及其作用机理。方法用MTT比色法检测PMN与HSC的粘附,分别用Cell-ELISA和RT-PCR法检测粘附分子ICAM-1和VCAM-1的蛋白及基因表达,用EMSA法检测NF-κB的活性。结果美洛昔康可显著的并以剂量依赖的方式抑制TNF-α(50 u·mL-1)和IL-1β(50 u·mL-1)作用12 h诱导的PMN与HSC粘附,其IC50分别为3.38×10-7和3.56×10-6 mol·L-1。进一步研究发现美洛昔康在1×10-6~1×10-5 mol·L-1时还可在蛋白水平及mRNA水平抑制TNF-α(50 u·mL-1)诱导的HSC细胞ICAM-1的表达,但对VCAM-1蛋白及mRNA表达均未见显著影响;同时美洛昔康还可显著抑制50 u·mL-1 TNF-α诱导的NF-κB的活化。结论美洛昔康抑制NF-κB的活化,进而抑制ICAM-1的表达可能是其抑制PMN与HSC粘附的机制之一。

     

    Abstract: AIMTo investigate the effect of meloxicam on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC), and to explore its mechanism. METHODSMTT colorimetry was used to determine the adhesion effect of PMN to HSC. Cell-ELISA and RT-PCR methods were used to determine the expression of ICAM-1 and VCAM-1. Nuclear transcription factor-kappa B (NF-κB) was measured by electrophoretic mobility shift assay (EMSA) method. RESULTS Meloxicam was found to effectively inhibit TNF-α (50 u·mL-1 for 12 h) and IL-1β (50 u·mL-1 for 12 h)-induced adhesion of PMN to HSC (IC50 3.38×10-7 mol·L-1 and 3.56×10-6 mol·L-1, respectively) in a concentration-dependent manner. ICAM-1 protein and mRNA expression induced by TNF-α (50 u·mL-1) were inhibited by meloxicam at 1×10-6~1×10-5 mol·L-1. The activation of NF-κB was also inhibited by meloxicam at 1×10-6~1×10-5 mol·L-1. CONCLUSIONThese results suggest that meloxicam inhibit TNF-α stimulated PMN-HSC adhesion and expression of ICAM-1 by suppressing the activity of NF-κB.

     

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