Abstract
Objective
We have previously shown that conjugated linoleic acid (CLA) regresses pre-established
murine atherosclerosis. Although the exact underlying mechanisms are unclear, accumulation
of macrophages and expression of inflammatory markers were reduced in atherosclerotic
plaques of CLA-fed mice, implicating the monocyte/macrophage as a target through which
CLA may mediate anti-atherosclerotic effects. CLA mediates its effect at least in
part via activation of the nuclear receptor, peroxisome proliferator activator receptor-γ
(PPARγ). In this study we investigate if CLA mediates anti-atherogenic effects via
modulation of monocyte/macrophage function and provide evidence for an additional
PPARγ-independent mechanism for CLA.
Methods and results
Migration of the human monocyte cell line THP-1, and primary blood monocytes (HPBMCs)
was assessed using transwell migration assays. Monocyte chemoattractant protein-1
(MCP-1) mediates chemotaxis via interaction with the chemokine (C–C motif)-2 receptor
(CCR-2), which is expressed on the monocyte cell surface, and is negatively regulated
by PPARγ agonists. Incubation of THP-1 monocytes with CLA-isomers and a PPARγ agonist
inhibited MCP-1-induced monocyte migration. Prior to monocyte recruitment, activated
platelets accumulate and release the contents of their secretory granules (“platelet-releasate”).
Here we demonstrate that platelet-releasate is a monocyte chemoattractant, and CLA,
but not the PPARγ agonist, inhibits platelet-releasate-induced migration of THP-1
and HPBMC monocytes. CLA-treatment also suppressed the inflammatory macrophage phenotype,
demonstrated by decreased induction of monocyte migration by CLA-treated macrophage-conditioned-media,
as well as by decreased cyclooxygenase (COX)-2 and cytosolic phospholipase-A2 (cPLA2) expression and MCP-1, prostaglandin E2 (PGE2) and matrix metalloprotease (MMP)-9 generation.
Conclusions
CLA-isomers inhibit monocyte migration and reduce the inflammatory output of the macrophage.
These mechanisms may contribute to the potent anti-atherosclerotic effects of CLA
in vivo.
Keywords
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Article info
Publication history
Published online: March 11, 2010
Accepted:
February 2,
2010
Received in revised form:
January 18,
2010
Received:
November 19,
2009
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
