Gallic acid promotes polarization of M2 macrophages through p38MAPK/STAT6 signaling pathway in vitro

Abstract

Abstract Background Interleukin-4 (IL-4)-stimulated M2 macrophage activation contributes to anti-inflammatory activity, tissue repair, and wound healing. Gallic acid (GA) the effect and underlying mechanism of gallic acid on the polarization of M2 macrophages remain to be elucidated. Methods and Results We constructed an M2 macrophages polarization model induced by 20 ng/mL IL-4, which were incubated alone (M0) or with GA at 10 µM, 20 µM, 30µM, and 40 µM for 24 h or pretreated with the p38MAPK inhibitor SB202190. We showed that F4/80+CD206+ M2 macrophages proportion (flow cytometry), IL-10, Arg1, and TGF-β1 expression levels (real-time PCR and Western blotting), and STAT6 and p38MAPK phosphorylation levels (Western blotting) were significantly (P < 0.01) higher in the GA group, as compared with the IL-4 group. After pretreatment with SB202190, M2-type macrophages proportion and their associated factors expression was significantly (P < 0.01) reduced, as compared with those in the GA group, but they were comparable (P > 0.05) with the IL-4 group. Conclusions Results of the present study suggest that GA promotes M2 macrophages polarization in a concentration-dependent manner, through the p38MAPK/STAT6 signaling pathway, providing new clues for cell-targeted therapies in M2 macrophages-mediated inflammatory diseases.