TY - JOUR
T1 - Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages
T2 - Evidence for a PPARγ-dependent mechanism
AU - Yu, Y.
AU - Correll, P. H.
AU - Vanden Heuvel, J. P.
N1 - Funding Information:
This research was funded by a grant from the Pennsylvania Department of Agriculture (ME 448435). The authors would like to thank Pharmanutrients for the donation of the CLA One mixture as well as offering support for the cytokine ELISA assays. Portions of this research were presented at the 2001 Society of Toxicology meeting.
PY - 2002/4/15
Y1 - 2002/4/15
N2 - Conjugated linoleic acid (CLA) is a dietary fatty acid that has received considerable attention due to its unique properties in rodent models including anti-cancer, anti-atherogenic and anti-diabetic effects. The effects of CLA are similar to those seen with ligands for peroxisome proliferator-activated receptor (PPARs), most notably of the PPARγ subtype. With the recent observation of a role for PPARγ in regulation of immune responses, we suspected that CLA could affect immune function, in particular macrophage activity. The goal of our study was to examine whether this dietary fatty acid has anti-inflammatory properties similar to those reported for PPARγ activators such as 15-deoxy prostaglandin J2 (PGJ2). In reporter assays, various CLA isomers activated PPARγ in RAW264.7 mouse macrophage (RAW) cells. CLA decreased the interferon-γ (IFNγ)-induced mRNA expression of mediators of inflammation including cyclooxygenase 2 (COX2), inducible NOS (iNOS), and tumor necrosis factor α (TNFα). Reporter assays also demonstrated reduced IFNγ-stimulated transcriptional activity of the iNOS and COX2 promoters by CLA. Consequently, CLA decreased the production of PGE2, TNFα and the inflammatory agent nitric oxide (NO) in RAW cells treated with IFNγ. Other pro-inflammatory cytokines such as IL-1β and IL-6 were similarly decreased by CLA treatment of RAW cells. In addition, various CLA isomers induced HL60 cell differentiation along the monocytic lineage as assessed by measuring expression of the cell surface marker CD14. This differentiation process, as well as the regulation of iNOS and COX2 by 15dPGJ2, is believed to involve PPARγ. Mutations of Leu468 and Glu471 to alanine in helix 12 of the ligand-binding domain of PPARγ resulted in a protein with strong dominant-negative activity (dnPPARγ). Transfecting dnPPARγ into RAW cells eliminated the ability of various CLA isomers to regulate the iNOS reporter construct. Taken together, these results suggest that CLA has anti-inflammatory properties that are mediated, at least in part, by the nuclear hormone receptor PPARγ.
AB - Conjugated linoleic acid (CLA) is a dietary fatty acid that has received considerable attention due to its unique properties in rodent models including anti-cancer, anti-atherogenic and anti-diabetic effects. The effects of CLA are similar to those seen with ligands for peroxisome proliferator-activated receptor (PPARs), most notably of the PPARγ subtype. With the recent observation of a role for PPARγ in regulation of immune responses, we suspected that CLA could affect immune function, in particular macrophage activity. The goal of our study was to examine whether this dietary fatty acid has anti-inflammatory properties similar to those reported for PPARγ activators such as 15-deoxy prostaglandin J2 (PGJ2). In reporter assays, various CLA isomers activated PPARγ in RAW264.7 mouse macrophage (RAW) cells. CLA decreased the interferon-γ (IFNγ)-induced mRNA expression of mediators of inflammation including cyclooxygenase 2 (COX2), inducible NOS (iNOS), and tumor necrosis factor α (TNFα). Reporter assays also demonstrated reduced IFNγ-stimulated transcriptional activity of the iNOS and COX2 promoters by CLA. Consequently, CLA decreased the production of PGE2, TNFα and the inflammatory agent nitric oxide (NO) in RAW cells treated with IFNγ. Other pro-inflammatory cytokines such as IL-1β and IL-6 were similarly decreased by CLA treatment of RAW cells. In addition, various CLA isomers induced HL60 cell differentiation along the monocytic lineage as assessed by measuring expression of the cell surface marker CD14. This differentiation process, as well as the regulation of iNOS and COX2 by 15dPGJ2, is believed to involve PPARγ. Mutations of Leu468 and Glu471 to alanine in helix 12 of the ligand-binding domain of PPARγ resulted in a protein with strong dominant-negative activity (dnPPARγ). Transfecting dnPPARγ into RAW cells eliminated the ability of various CLA isomers to regulate the iNOS reporter construct. Taken together, these results suggest that CLA has anti-inflammatory properties that are mediated, at least in part, by the nuclear hormone receptor PPARγ.
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U2 - 10.1016/S1388-1981(02)00126-9
DO - 10.1016/S1388-1981(02)00126-9
M3 - Article
C2 - 12020636
AN - SCOPUS:0037089259
SN - 1388-1981
VL - 1581
SP - 89
EP - 99
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 3
ER -
