Apigenin attenuated sepsis induced acute lung injury via polarizing macrophage towards M2 by blocking miR-146a →TLR7 interaction.

TLR7 (Toll-like receptor 7) has been indicated as an important sensor for single -stranded RNA contributes to systemic inflammation and mortality in acute lung injury (ALI), which is an acute diffuse inflammatory lung injury. Cumulative results show that macrophages contribute to the development and progression of ALI through the secretion of inflammatory cytokines/chemokines. Here we show that macrophage polarizes towards M1 phenotype and TLR7 signaling is activated in septic mice. Moreover, TLR7 deficiency promotes macrophage polarized towards M2 phenotype and attenuates ALI. Strikingly, the natural product of flavone apigenin (Xu et al., 2017 [1]) significantly improves sepsis-induced lung inflammation and lung injury via inhibiting inflammatory macrophages in a TLR7-dependent manner. Mechanically, Api blocked the binding of TLR7 with its agonist miR-146a. This finding reveals TLR7 is an important therapeutic target and Api as a modulator of TLR7 is a potential lead compound for treatment of septic diseases and inflammation related diseases.