Mesenchymal stem cell-secreted prostaglandin E2 ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization

Abstract Background Acute liver failure (ALF) is an acute inflammatory disease with high mortality. Previous preclinical and clinical trials have confirmed that mesenchymal stem cell (MSC) a promising therapeutic approach; however, the effect not satisfied as underlying molecular mechanisms of MSC in treating ALF remain unclear. Methods isolated from 4- to 6-week-old C57BL/6 mice were used treat ALF. Histological serological parameters analyzed evaluate efficacy MSC. We explored mechanism treatment by detecting response hepatocyte death. Results In this study, we found potential on dependent secretion prostaglandin E 2 (PGE ), bioactive lipid. MSC-derived PGE inhibited TGF-β-activated kinase 1 (TAK1) signaling NLRP3 inflammasome activation macrophages decrease production cytokines. Meanwhile, could be induced anti-inflammatory (M2) via STAT6 mechanistic target rapamycin (mTOR) signaling, which then promote resolution limit injury. Finally, administrating EP4 antagonist significantly ameliorated ability MSC, promoted inflammation decreased M2 macrophages. Conclusions Our results indicate might novel important mediator ALF, through inhibiting