Anti-inflammatory inhibition of endothelial cell adhesion molecule expression by flavone derivatives.
Endothelial expression of cell adhesion molecules (CAM) including VCAM-1, E-selectin, and PECAM-1 plays a leading role in atherosclerosis. Phenolic flavones have been shown to have an anti-inflammatory property. This study examines whether 3',4'-dimethoxy-7-hydroxyflavone (methoxyflavone) and 2',3',7-trihydroxyflavone (hydroxyflavone) inhibited monocyte adhesion to TNF-alpha-activated endothelium via reduction of CAM expression in human umbilical vein endothelial cells (HUVEC). In stimulated HUVEC the expression of VCAM-1 and E-selectin was enhanced with increasing mRNA levels. Methoxyflavone markedly interfered with the THP-1 monocyte adhesion to TNF-alpha-stimulated HUVEC. At concentrations of > or =25 microM, methoxyflavone blocked the induction of VCAM-1 but not that of E-selectin on the activated HUVEC. Immunocytochemical staining showed that methoxyflavone modestly inhibited PECAM-1 expression induced by TNF-alpha. In contrast, hydroxyflavone minimally inhibited TNF-alpha-stimulated E-selectin expression without affecting VCAM-1 level. The inhibitory effect of methoxyflavone on THP-1 adhesion to HUVEC appears to be greater than that of hydroxyflavone, most likely due to a greater inhibition of CAM expression. Thus, some flavone derivatives containing methoxy groups may have therapeutic potential attenuating inflammatory response-related atherosclerosis.
Kwon
Hyang-Mi
HM
Department of Food and Nutrition and Silver Biotechnology Research Center, Hallym University, Chuncheon, Republic of Korea.
Choi
Yean-Jung
YJ
Jeong
Yu-Jin
YJ
Kang
Sang-Wook
SW
Kang
Il-Jun
IJ
Lim
Soon Sung
SS
Kang
Young-Hee
YH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics*; D002478:Cells, Cultured; D019040:E-Selectin / Q000032:analysis / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D047309:Flavones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D009000:Monocytes / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D047309:Flavones; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1