MAPKs control the expression of a novel gene set that defines de activation of human anti-inflammatory macrophages

LPS treatment is considered as the paradigmatic stimulus for acquisition of the classical macrophage polarization/activation state. However, this definition does not take into account the influence that other macrophage differentiating/priming factors might have on the LPS response. In spite of the pathophysiological relevance of the response of M-CSF-dependent anti-inflammatory human macrophages (M-MØ) to endogenous and pathogenic stimuli, detailed analysis of the gene signature of activated anti-inflammatory M-CSF-dependent macrophages remained to be determined. We have now compared the early transcriptional signatures of human GM-MØ and M-MØ in response to macrophage-activating agents and identified a unique gene set acquired upon activation of anti-inflammatory M-MØ. Macrophages were differentiated from peripheral blood monocytes from 3 healthy donors with M-CSF or GM-CSF to generate anti-inflammatory (M-MØ) or pro-inflammatory (GM-MØ) macrophages, respectively. M-MØ and GM-MØ were stimulated with 10ng/ml LPS for 4h.