BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis. (January 2018)

• Record Type: Journal Article
• Authors: Chen, Lu; Lu, Feng-bin; Chen, Da-zhi; Wu, Jin-lu; Hu, En-de; Xu, Lan-man; Zheng, Ming-hua; Li, Hui; Huang, Yu; Jin, Xiao-ya; Gong, Yue-wen; Lin, Zhuo; Wang, Xiao-dong; Chen, Yong-ping
• Is Part Of: Molecular immunology. Volume 93(2018:Jan.)
• Page Start: 38
• Page End: 46
• Publication Date: 2018-01
• Subjects: AIH autoimmune hepatitis -- EAH experimental autoimmune hepatitis -- BMSCs bone marrow derived mesenchymal stem cells -- miR 223 microRNA 223 -- LPS lipopolysaccharide -- ATP adenosine triphosphate -- ALT alanine transaminase -- AST aspartate transaminase -- NLRP3 NLR pyrin domain containing 3 -- ASC apoptotic specklike protein containing CARD -- EVs extracellular vesicles -- IL-6 interleukin 6 -- TNF-α Tumor Necrosis Factor α -- IL-1β interleukin 1β -- IL-17 interleukin 17 -- PBS phosphate-buffered saline -- DMEM Dulbecco modified Eagle medium -- ITS insulin, transferrin and selenium -- CM culture medium -- BSA bovine serum albumin -- H&E hematoxylin and eosin -- RIPA radio immunoprecipitation assay -- PMSF phenylmethanesulfonyl fluoride -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- PCR polymerase chain reaction -- LDH lactate dehydrogenase -- ANOVA analysis of variance -- CAPS cryopyrin-associated periodic syndrome -- FMF Familial Mediterranean fever; Exosomes -- Hepatic damage -- AIH -- miRNA -- NLRP3; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.11.008
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: BMSCs-exo attenuated liver damage induced by autoimmune hepatitis. BMSCs-exo decreased serum levels of ALT, AST and pro-inflammatory cytokines. BMSCs-exo downregulated the expression of NLRP3 and Caspase-1. miR-223 contributed to the function of BMSCs-exo. 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-exo miR−223(+) 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-exo miR−223(+) at both protein and mRNA levels in mice and hepatocytes. Moreover, BMSCs-exo miR−223(−) reverses the effects of BMSCs-exo and BMSCs-exo miR−223(+) 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.