Unlike PPARγ, PPARα or PPARβ/δ 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 in "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 PPAR gamma promotes the differentiation of monocytes into anti-inflammatory M2 macrophages in humans and mice, while a role for PHAR beta/delta in this process has been reported only in mice and no data are available for PPAR alpha. Here, we show that in contrast to PPAR gamma, expression of PPAR alpha and PPAR beta/delta overall does not correlate with the expression of M2 markers ill human atherosclerotic lesions. whereas a positive correlation with genes of lipid metabolism exists. Moreover, Unlike PPAR gamma, PPAR alpha or PPAR beta/delta activation does not influence human monocyte differentiation into M2 macrophages in vitro. Thus, PPAR alpha and PPAR beta/delta do not appear to modulate the alternative differentiation Of human macrophages. (C) 2009 Elsevier Inc. All rights reserved.