Docosahexaenoic Acid Induces M2 Macrophage Polarization through Peroxisome Proliferator-activated Receptor γ Activation

Abstract

Impaired resolution of acute inflammation leads to chronic inflammatory diseases such as atherosclerosis, asthma and arthritis. For complete resolution of inflammation, clearance of apoptotic neutrophils by macrophage phagocytosis, called efferocytosis, is critical. During resolution of inflammation, macrophages, especially alternatively activated or M2, play a key role in efferocytosis. In the process of macrophage differentiation, peroxisome proliferator-activated receptor γ (PPARγ) activation promotes M2 polarization. In the present study, I found that docosahexaenoic acid (DHA) polarized murine macrophage-like RAW264.7 cells toward M2 by upregulating PPARγ expression. DHA-induced M2 activation resulted in enhancement of efferocytosis. However, knockdown of PPARγ abolished the effect of DHA on M2 polarization and efferocytosis. Lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines was significantly downregulated by DHA, suggesting that DHA alters the macrophage phenotype in favor of M2 while suppressing M1 polarization. Moreover, addition of DHA restored the efferocytic ability of LPS-treated RAW264.7 cells, suggesting that M2 macrophages are more effective for engulfing apoptotic cells than M1. In conclusion, DHA can promote resolution of inflammation by facilitating efferocytosis driven by M2 macrophage polarization.