Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid

Alan Arthur Sneddon, Ewan McLeod, Klaus Wilfried Juergen Wahle, John Arthur

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Monocyte-endothelium interaction is key to many acute and chronic inflammatory diseases. We have investigated the factors regulating monocyte attachment to cytokine-activated human umbilical vein endothelial cells (HUVEC) and the modulatory effect of the polyunsaturated fatty acid (PUFA), conjugated linoleic acid (CLA) in this process. Both TNF-alpha and IL-1 beta induced HUVEC platelet-activating factor (PAF) production and PAF was required for subsequent firm THP-1 monocyte adhesion since it was inhibited by both PAF receptor antagonists (BN-52021 or CV-6209) and a PAF synthesis inhibitor (sanguinarine). CLA inhibited the binding of both THP-1 and isolated human peripheral blood monocytes to HUVEC by up to 40% with the CLA t10,c12 isomer suppressing adhesion dose-dependently. Investigation into the mechanism involved demonstrated that with IL-1 beta, VCAM-1 and ICAM-1 levels and pro-inflammatory cytokine expression were largely unaffected by CLA. Through the use of PAF receptor antagonists and PAF synthesis inhibitors, CLA was shown to inhibit cytokine-induced binding by suppressing PAF production. Direct assay of PAF levels confirmed this result. We conclude that endothelial-generated PAF plays a central role in cytokine-induced monocyte adherence to endothelium and that the anti-inflammatory action of PUFAs such as CLA in suppressing monocyte-endothelial interaction is mediated through attenuation of pro-inflammatory phospholipids such as PAF. (c) 2006 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)793-801
Number of pages9
JournalBiochimica et Biophysica Acta. Molecular and Cell Biology of Lipids
Volume1761
Issue number7
DOIs
Publication statusPublished - Jul 2006

Keywords

  • CLA
  • inflammation
  • PUFA
  • phospholipid
  • cell adhesion
  • PAF antagonist
  • tumor necrosis factor
  • polyunsaturated fatty acids
  • Kappa-B
  • transendothelial migration
  • factor alpha
  • atherosclerosis
  • release
  • VCAM-1
  • interleukin-1-Alpha
  • metabolites
  • Inflammation
  • Phospholipid
  • Cell adhesion

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