Hypoxia/Reoxygenation Injury By Inducing Polarization Of M2-Type Macropahges And Identification

Objective: To investigate the protective effect of interleukin-37(IL-37)on hepatocyte injury with hypoxia/reoxygenation(H/R)by promoting polarization of M2-type macrophages and its related molecular mechanisms.Methods: Real-time fluorescent quantitative PCR and western blot were used to detect the expression of IL-37 mRNA and protein in human monocyte-macrophage THP-1 cell with different polarizations.The lentivirus with IL-37 gene was infected into THP-1 cell.The expression of CD206 and CD86 mRNA was detected by real-time fluorescence quantitative PCR.THP-1 cells and LO2 cells were co-cultured by transwell and performed H/R treatment.The survival rate and apoptosis rate of LO2 cells were detected.The levels of alanine transaminase(ALT)and aspartate aminotransferase(AST)in culture medium were measured.The expression of STAT6 and its phosphorylated protein in THP-1 cells were detected by western blot.Results: The expression of IL-37 mRNA and protein was up-regulated in M2 macrophages.IL-37 promotes the polarization of M2-type macropahges.M2-type macrophages induced by IL-37 were co-cultured with LO2 cells and performed H/R treatment,the survival rate was significantly increased(P = 0.015)while the apoptotic rate,ALT level and AST level were significantly decreased(P < 0.001).Western blot showed that the phosphorylation of STAT6 protein in THP-1 cells overexpressing IL-37 was up-regulated(P <0.01).Conclusion: IL-37 can induce polarization of M2-type macrophages and protect hepatocytes against hypoxia/reoxygenation injury.The mechanism may be related to STAT6 Signal pathways.