PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties.
Th1 cytokines promote monocyte differentiation into proatherogenic M1 macrophages, while Th2 cytokines lead to an "alternative" anti-inflammatory M2 macrophage phenotype. Here we show that in human atherosclerotic lesions, the expression of M2 markers and PPARgamma, a nuclear receptor controlling macrophage inflammation, correlate positively. Moreover, PPARgamma activation primes primary human monocytes into M2 differentiation, resulting in a more pronounced anti-inflammatory activity in M1 macrophages. However, PPARgamma activation does not influence M2 marker expression in resting or M1 macrophages, nor does PPARgamma agonist treatment influence the expression of M2 markers in atherosclerotic lesions, indicating that only native monocytes can be primed by PPARgamma activation to an enhanced M2 phenotype. Furthermore, PPARgamma activation significantly increases expression of the M2 marker MR in circulating peripheral blood mononuclear cells. These data demonstrate that PPARgamma activation skews human monocytes toward an anti-inflammatory M2 phenotype.
Institut Pasteur de Lille, F-59019 Lille, France; Inserm, U545, F-59019 Lille, France.
M Amine
MA
Bouhlel
Bruno
B
Derudas
Elena
E
Rigamonti
Rébecca
R
Dièvart
John
J
Brozek
Stéphan
S
Haulon
Christophe
C
Zawadzki
Brigitte
B
Jude
Gérard
G
Torpier
Nikolaus
N
Marx
Bart
B
Staels
Giulia
G
Chinetti-Gbaguidi
D001577:Benzophenones / Q000494:pharmacology; D015415:Biomarkers; D001773:Blood Cells / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005487:Foam Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D010641:Phenotype; D013234:Stem Cells / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D001577:Benzophenones; D015415:Biomarkers; D047495:PPAR gamma; D014443:Tyrosine; C120099:GW 1929