Conjugated linoleic acids have no effect on TNF alpha-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells.
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.
Schleser
Sabine
S
Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhaldenstrasse 26, D-06108 Halle/Saale, Germany.
Ringseis
Robert
R
Eder
Klaus
K
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
D015815:Cell Adhesion Molecules; D018925:Chemokines; D044243:Linoleic Acids, Conjugated; D014409:Tumor Necrosis Factor-alpha