Quercetin confers protection of murine sepsis by inducing macrophage M2 polarization via the TRPM2 dependent calcium influx and AMPK/ATF3 activation

Abstract

M2 macrophage polarization plays a crucial role in counteracting inflammatory disorders such as sepsis. Quercetin is a dietary flavonoid that possesses robust anti-inflammatory properties. However, it is not known whether quercetin takes effects by directly promoting M2 polarization in macrophages. In this study, we observed that quercetin enhanced macrophage M2 polarization and exerted anti-inflammatory activity in LPS stimulated murine peritoneal macrophages. Moreover, quercetin triggered TRPM2 dependent calcium influx and induced calcium dependent activation of AMPKα and ATF3, both were required to mediate M2 macrophage polarization and facilitate the anti-inflammatory activity by quercetin. In a murine endotoxaemia model, quercetin improved survival and ameliorated acute lung injury. Quercetin also induced AMPKα phosphorylation, upregulated ATF3 expression and promoted M2 macrophage polarization in model mice. In conclusion, our results suggest that quercetin promotes macrophage M2 polarization and confers protection of murine sepsis by inducing calcium dependent activation of the AMPK-ATF3 pathway.

Keywords

• Quercetin
• Sepsis
• Macrophage polarization
• TRPM2
• AMPK
• ATF3