Inhibitory effect of meloxicam on human polymorphonuclear leukocyte adhesion to human synovial cell.
OBJECTIVE
To investigate the effect of meloxicam on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC), and to explore its mechanism.


METHODS
MTT 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-kappa B) was measured by electrophoretic mobility shift assay (EMSA) method.


RESULTS
Meloxicam was found to effectively inhibit TNF-alpha (50 u.mL-1 for 12 h) and IL-1 beta (50 u.mL-1 for 12 h)-induced adhesion of PMN to HSC (IC50 3.38 x 10(-7) mol.L-1 and 3.56 x 10(-6) mol.L-1, respectively) in a concentration-dependent manner. ICAM-1 protein and mRNA expression induced by TNF-alpha (50 u.mL-1) were inhibited by meloxicam at 1 x 10(-6)-1 x 10(-5) mol.L-1. The activation of NF-kappa B was also inhibited by meloxicam at 1 x 10(-6)-1 x 10(-5) mol.L-1.


CONCLUSIONS
These results suggest that meloxicam inhibit TNF-alpha stimulated PMN-HSC adhesion and expression of ICAM-1 by suppressing the activity of NF-kappa B.
Li
Liang-cheng
LC
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Hou
Qi
Q
Guo
Ying
Y
Cheng
Gui-fang
GF
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D000077239:Meloxicam; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013583:Synovial Membrane / Q000166:cytology*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D012333:RNA, Messenger; D013843:Thiazines; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000077239:Meloxicam