PMID- 20223456
OWN - NLM
STAT- MEDLINE
DCOM- 20101026
LR  - 20181201
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 211
IP  - 1
DP  - 2010 Jul
TI  - Conjugated linoleic acid suppresses the migratory and inflammatory phenotype of 
      the monocyte/macrophage cell.
PG  - 96-102
LID - 10.1016/j.atherosclerosis.2010.02.003 [doi]
AB  - 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. 
      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 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.
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - McClelland, Sarah
AU  - McClelland S
AD  - School of Biomedical and Biomolecular Science, UCD Conway Institute, University 
      College Dublin, Ireland.
FAU - Cox, Clare
AU  - Cox C
FAU - O'Connor, Roisin
AU  - O'Connor R
FAU - de Gaetano, Monica
AU  - de Gaetano M
FAU - McCarthy, Cathal
AU  - McCarthy C
FAU - Cryan, Lorna
AU  - Cryan L
FAU - Fitzgerald, Des
AU  - Fitzgerald D
FAU - Belton, Orina
AU  - Belton O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100210
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromans)
RN  - 0 (Linoleic Acids, Conjugated)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Thiazolidinediones)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - I66ZZ0ZN0E (Troglitazone)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Cell Movement/*drug effects
MH  - Chemokine CCL2/metabolism
MH  - Chromans/pharmacology
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/metabolism
MH  - Humans
MH  - Linoleic Acids, Conjugated/*pharmacology
MH  - Macrophages/*drug effects
MH  - Matrix Metalloproteinase 9/biosynthesis
MH  - Monocytes/*drug effects
MH  - PPAR gamma
MH  - Phospholipases A2/biosynthesis
MH  - Receptors, CCR2/physiology
MH  - Thiazolidinediones/pharmacology
MH  - Troglitazone
EDAT- 2010/03/13 06:00
MHDA- 2010/10/27 06:00
CRDT- 2010/03/13 06:00
PHST- 2009/11/19 00:00 [received]
PHST- 2010/01/18 00:00 [revised]
PHST- 2010/02/02 00:00 [accepted]
PHST- 2010/03/13 06:00 [entrez]
PHST- 2010/03/13 06:00 [pubmed]
PHST- 2010/10/27 06:00 [medline]
AID - S0021-9150(10)00101-2 [pii]
AID - 10.1016/j.atherosclerosis.2010.02.003 [doi]
PST - ppublish
SO  - Atherosclerosis. 2010 Jul;211(1):96-102. doi: 
      10.1016/j.atherosclerosis.2010.02.003. Epub 2010 Feb 10.