title: Inhibitory effects of luteolin on transendothelial migration of monocytes and formation of lipid-laden macrophages.
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.
  
  
  CONCLUSIONS
  Luteolin may qualify as an antiatherogenic agent in LDL systems, which may have implications for strategies attenuating monocyte/macrophage dysfunction-related atherosclerosis.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Dong Shoo
authors.initials: DS
authors.lastname: Kim
authors.forename: Hyun-Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism* / Q000517:prevention & control; D018821:CD18 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*
chemical_list: D018821:CD18 Antigens; D016207:Cytokines; D008077:Lipoproteins, LDL; D062793:Occludin; D010936:Plant Extracts; D010982:Platelet-Derived Growth Factor; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein; D020780:Matrix Metalloproteinase 9; D047311:Luteolin