Inhibitory effects of luteolin on transendothelial migration of monocytes and formation of lipid-laden macrophages

Objective: Because of an initial activation of proinflammatory cytokines that facilitates leukocyte transmigration, atherosclerosis is a chronic inflammatory disease and its severity is accelerated by the occurrence of complex interactions of oxidatively modified low-density lipoprotein (LDL) with monocyte-derived macrophages. Methods: The present study investigated whether luteolin suppresses adheren junction-associated monocyte transmigration and platelet-derived growth factor-BB-mediated foam cell formation. The involvement of monocyte integrins and macrophage scavenger receptors (SRs) also was determined. Results: Luteolin, non-toxic at 1 to 20 mu mol/L, blocked the monocyte-endothelium interactions by inhibiting the cytokine-associated monocyte induction of integrin-beta 2. Luteolin retarded the transendothelial migration of monocytes by firmly localizing the occludin present in paracellular endothelial junctions and by blunting the monocyte activity of matrix-degrading matrix metalloproteinase-9. Treatment with luteolin showed inhibitory effects on oxidized LDL-triggered foam cell formation by decreasing SR-A and SR-B1 induction in THP-1 cell-derived macrophages, which was confirmed by Oil red O and 1,1'-dioctadecy1-3,3,3',3'-tetramethylindocarbocyanine perchlorate staining. Furthermore, luteolin attenuated the oxidized LDL-induced macrophage secretion of platelet-derived growth factor-BB, entailing the induction of SR-A and SR-B1. These results demonstrate that luteolin encumbered monocyte cytokine-instigated endothelial transmigration and oxidized LDL-elicited macrophage foam cell formation. Conclusion: Luteolin may qualify as an antiatherogenic agent in LDL systems, which may have implications for strategies attenuating monocyte/macrophage dysfunction-related atherosclerosis. (C) 2012 Elsevier Inc. All rights reserved.