PPARγ 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 PPAR gamma, a nuclear receptor controlling macrophage inflammation, correlate positively. Moreover, PPAR gamma activation primes primary human monocytes into M2 differentiation, resulting in a more pronounced anti-inflammatory activity in M1 macrophages. However, PPAR gamma activation does not influence M2 marker expression in resting or M1 macrophages, nor does PPAR gamma agonist treatment influence the expression of M2 markers in atherosclerotic lesions, indicating that only native monocytes can be primed by PPAR gamma activation to an enhanced M2 phenotype. Furthermore, PPAR gamma activation significantly increases expression of the M2 marker MR in circulating peripheral blood mononuclear cells. These data demonstrate that PPAR gamma activation skews human monocytes toward an anti-inflammatory M2 phenotype.