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-α and IL-1β 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-1β, 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.
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More From: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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