title: Conjugated linoleic acid suppresses the migratory and inflammatory phenotype of the monocyte/macrophage cell.
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-gamma (PPARgamma). In this study we investigate if CLA mediates anti-atherogenic effects via modulation of monocyte/macrophage function and provide evidence for an additional PPARgamma-independent mechanism for CLA.
  
  
  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 PPARgamma agonists. Incubation of THP-1 monocytes with CLA-isomers and a PPARgamma 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 PPARgamma 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.
authors.affiliation: School of Biomedical and Biomolecular Science, UCD Conway Institute, University College Dublin, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: McClelland
authors.forename: Clare
authors.initials: C
authors.lastname: Cox
authors.forename: Roisin
authors.initials: R
authors.lastname: O'Connor
authors.forename: Monica
authors.initials: M
authors.lastname: de Gaetano
authors.forename: Cathal
authors.initials: C
authors.lastname: McCarthy
authors.forename: Lorna
authors.initials: L
authors.lastname: Cryan
authors.forename: Des
authors.initials: D
authors.lastname: Fitzgerald
authors.forename: Orina
authors.initials: O
authors.lastname: Belton
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects*; D047495:PPAR gamma; D054467:Phospholipases A2 / Q000096:biosynthesis; D054390:Receptors, CCR2 / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D018932:Chemokine CCL2; D002839:Chromans; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D054390:Receptors, CCR2; D045162:Thiazolidinediones; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; D020780:Matrix Metalloproteinase 9; D000077288:Troglitazone; D015232:Dinoprostone