Unlike PPARgamma, PPARalpha or PPARbeta/delta activation does not promote human monocyte differentiation toward alternative macrophages.
Macrophages adapt their response to micro-environmental signals. While Th1 cytokines promote pro-inflammatory M1 macrophages, Th2 cytokines promote an "alternative" anti-inflammatory M2 macrophage phenotype. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors expressed in macrophages where they control the inflammatory response. It has been shown that PPARgamma promotes the differentiation of monocytes into anti-inflammatory M2 macrophages in humans and mice, while a role for PPARbeta/delta in this process has been reported only in mice and no data are available for PPARalpha. Here, we show that in contrast to PPARgamma, expression of PPARalpha and PPARbeta/delta overall does not correlate with the expression of M2 markers in human atherosclerotic lesions, whereas a positive correlation with genes of lipid metabolism exists. Moreover, unlike PPARgamma, PPARalpha or PPARbeta/delta activation does not influence human monocyte differentiation into M2 macrophages in vitro. Thus, PPARalpha and PPARbeta/delta do not appear to modulate the alternative differentiation of human macrophages.
Bouhlel
Mohamed Amine
MA
Univ Lille Nord de France, F-59000 Lille, France.
Brozek
John
J
Derudas
Bruno
B
Zawadzki
Christophe
C
Jude
Brigitte
B
Staels
Bart
B
Chinetti-Gbaguidi
Giulia
G
D050197:Atherosclerosis / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D047493:PPAR alpha / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D047494:PPAR delta / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D048068:PPAR-beta / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics
D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D048068:PPAR-beta