Liang-Ge-San drives macrophages toward M2 polarization for alleviating lipopolysaccharide-induced acute lung injury via activating the miR-21/PTEN axis

Abstract

Acute lung injury (ALI) has high clinical mortality currently and no specific drugs available for its treatment. Although Liang-Ge-San (LGS), a traditional Chinese medicine formula, is known to promote inflammation resolution and shorten hospitalization duration of ALI, the mechanism is still unclear. Our results demonstrated that LGS regulated the dynamic balance of macrophage polarization as reflected by up-regulating the expression of anti-inflammatory factors (CD206, Arg-1 and IL-10) in advance to counteract the high expression of pro-inflammatory factors (CD86, iNOS, IL-6 and TNF-α) in vitro. MiR-21 concentration was elevated in LPS-challenged RAW264.7 cells and ALI mice. Moreover, the overexpression of miR-21 mimicked the anti-inflammatory effects of LGS, whereas a miR-21 inhibitor abolished the protective effects of LGS in vitro. Most importantly, LGS protected ALI mice from LPS which could be counteracted by the treatment of miR-21 antagomir. Furthermore, LGS could inhibit the transcriptional activity and protein expression of PTEN by up-regulating miR-21. In summary, LGS functions by regulating the miR-21/PTEN axis to induce a shift in macrophages from a pro-inflammatory phenotype to an anti-inflammatory phenotype, thereby alleviating LPS-induced ALI. This study supports the clinical evidence of LGS in the treatment of ALI.