title: Conjugated linoleic acids have no effect on TNF alpha-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells.
abstract: Leukocyte recruitment and adhesion to the endothelium are critical steps in the early phase of atherosclerosis. Synthetic ligands of peroxisome proliferator-activated receptors (PPARs) were shown to reduce cytokine-stimulated leukocyte-endothelial cell interactions by inhibiting the NF-kappaB mediated inflammatory response. Conjugated linoleic acids (CLA), which are natural ligands of PPARs, were demonstrated to have anti-inflammatory and anti-atherogenic properties in vivo. With a view to elucidating the anti-atherogenic mechanisms of CLA, the present study aimed to explore the effects of cis-9, trans-11 CLA and trans-10, cis-12 CLA on cytokine-induced chemokine release, surface expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and U937 monocyte adhesion in human aortic endothelial cells (HAEC). Treatment of HAECs with 2 ng/mL of TNFalpha markedly increased expression of adhesion molecules, U937 monocyte adhesion, and release of the monocyte chemoattractant protein (MCP)-1. However, treatment of HAECs with either CLA isomer or linoleic acid did not modulate the cytokine-induced expression of ICAM-1, VCAM-1, and E-selectin, U937 cell adhesion and MCP-1 release. In addition, both CLA isomers and linoleic acid slightly increased PPARgamma DNA-binding activity, but did not alter DNA-binding activity of NF-kappaB. In conclusion, CLA isomers showed no effect on cytokine-induced monocyte-endothelial cell interactions and on the molecular mechanisms regulating these processes in HAEC. This study suggests that anti-atherogenic effects of CLA observed in vivo are probably not mediated by reduced monocyte-endothelial cell interactions.
authors.affiliation: Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhaldenstrasse 26, D-06108 Halle/Saale, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schleser
authors.forename: Robert
authors.initials: R
authors.lastname: Ringseis
authors.forename: Klaus
authors.initials: K
authors.lastname: Eder
mesh_terms: D000328:Adult; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D020298:U937 Cells
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D044243:Linoleic Acids, Conjugated; D014409:Tumor Necrosis Factor-alpha