Inhibitory effect and mechanism of action of sanggenon C on human polymorphonuclear leukocyte adhesion to human synovial cells.
OBJECTIVE
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 MTT colorimetry. Cell-ELISA and RT-PCR methods were used to examine the expression of adhesion molecules ICAM-1 and VCAM-1. Activation of nuclear factor-kappa B(NF-kappaB) was measured by electrophoretic mobility shift assays(EMSA) method.


RESULTS
Sanggenon C effectively inhibited TNF-alpha (50 kU/L for 12 h) and IL-1beta (50 kU/L for 12 h) induced adhesion of PMN to HSC (IC50 27.29 nmol/L and 54.45 nmol/L, respectively) in a concentration-dependent manner. Adhesion molecule VCAM-1 surface protein and mRNA expression induced by TNF-alpha 50 kU/L were significantly inhibited by sanggenon C, nevertheless, for ICAM-1 only surface protein expression being inhibited. The activation of NF-kappaB was also extensively inhibited by sanggenon C.


CONCLUSIONS
Sanggenon C inhibited TNF-alpha -stimulated PMN-HSC adhesion and expression of VCAM-1 by suppressing the activation of NF-kappaB.
Li
Liang-Cheng
LC
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China. chenggf@imm.ac.cn
Shen
Fang
F
Hou
Qi
Q
Cheng
Gui-Fang
GF
D001572:Benzofurans / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D031625:Morus / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D018517:Plant Roots / Q000737:chemistry; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001572:Benzofurans; D002867:Chromones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C477157:sanggenone C