Conjugated linoleic acids have no effect on TNF alpha-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells

Atherosclerosis. 2006 Jun;186(2):337-44. doi: 10.1016/j.atherosclerosis.2005.08.018. Epub 2005 Oct 10.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aorta / cytology*
  • Aorta / drug effects
  • Aorta / metabolism
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules* / biosynthesis
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemokines / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Linoleic Acids, Conjugated / pharmacology*
  • Monocytes / cytology*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Tumor Necrosis Factor-alpha / physiology*
  • U937 Cells

Substances

  • Cell Adhesion Molecules
  • Chemokines
  • Linoleic Acids, Conjugated
  • Tumor Necrosis Factor-alpha