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.