Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8648609 | Molecular Immunology | 2018 | 9 Pages |
Abstract
Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte. Before the experiments, BMSCs were infected with pre-miR-223 and transfected with miR-223 inhibitor respectively. Exosomes from bone marrow stem cells were isolated by ultracentrifugation. Liver injury was evaluated by serum levels of ALT and AST as well as liver histology. Inflammation and cell death were examined by inflammatory cytokines and lactase dehydrogenase respectively. Both BMSCs-exo and BMSCs-exomiRâ223(+) significantly reversed either S100 or LPS/ATP induced injury in mice and hepatocytes. Meanwhile, the expressions of cytokines, NLRP3 and caspase-1 were also downregulated by BMSCs-exo and BMSCs-exomiRâ223(+) at both protein and mRNA levels in mice and hepatocytes. Moreover, BMSCs-exomiRâ223(â) reverses the effects of BMSCs-exo and BMSCs-exomiRâ223(+) in mouse AIH and in hepatocytes. In conclusion, bone marrow stem cell derived exosomes can protect liver injury in an experimental model of autoimmune hepatitis and the mechanism could be related to exosomal miR-223 regulation of NLRP3 and caspase-1.
Keywords
FMFBMSCsGAPDHALTPMSFASCIL-1βRIPAITSIL-17CAPSDMEMIL-6LPSAIHPBSNLRP3Dulbecco Modified Eagle MediumEVSExperimental autoimmune hepatitisEAHBSAH&EAdenosine TriphosphateATPRadio immunoprecipitation assayASTHepatic damagealanine transaminasebovine serum albuminExosomesinterleukin 17interleukin 1βinterleukin 6Familial Mediterranean feveranalysis of varianceANOVAaspartate transaminasetumor necrosis factor αExtracellular vesiclesbone marrow derived mesenchymal stem cellsCryopyrin-associated periodic syndromeTNF-αPhenylmethanesulfonyl fluoridelactate dehydrogenaseLDHlipopolysaccharidePhosphate-buffered salineculture mediumMiRNAHematoxylin and EosinAutoimmune hepatitispolymerase chain reactionPCRglyceraldehyde-3-phosphate dehydrogenase
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Authors
Lu Chen, Feng-bin Lu, Da-zhi Chen, Jin-lu Wu, En-de Hu, Lan-man Xu, Ming-hua Zheng, Hui Li, Yu Huang, Xiao-ya Jin, Yue-wen Gong, Zhuo Lin, Xiao-dong Wang, Yong-ping Chen,