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

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2012-10, Vol.28 (10), p.1044-1054
• Main Authors: Kim, Min Soo, B.S, Kim, Dong Shoo, M.S, Kim, Hyun-Sung, B.S, Kang, Sang-Wook, Ph.D, Kang, Young-Hee, Ph.D
• Format: Article
• Language: English
• Subjects: Antioxidants; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - prevention & control; Biological and medical sciences; CD18 Antigens - metabolism; Cell adhesion & migration; Cell Line, Tumor; chronic diseases; Cytokines - metabolism; disease severity; Endothelium; Feeding. Feeding behavior; Foam cells; Foam Cells - drug effects; Foam Cells - metabolism; Free radicals; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; gelatinase A; Human Umbilical Vein Endothelial Cells; Humans; Integrin; integrins; Lipoproteins; Lipoproteins, LDL - metabolism; low density lipoprotein; Luteolin; Luteolin - pharmacology; Luteolin - therapeutic use; Matrix Metalloproteinase 9 - metabolism; Monocyte transendothelial migration; monocytes; Monocytes - drug effects; Monocytes - metabolism; Occludin; Occludin - metabolism; Perchlorate; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plasma; Platelet-Derived Growth Factor - secretion; Polyphenols; receptors; Receptors, Scavenger - metabolism; Rodents; Scavenger receptor; Smooth muscle; Transendothelial and Transepithelial Migration - drug effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2011.12.003

Abstract 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 μmol/L, blocked the monocyte–endothelium interactions by inhibiting the cytokine-associated monocyte induction of integrin-β2. 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′-dioctadecyl-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.