Interleukin‐10 secreted by mesenchymal stem cells attenuates acute liver failure through inhibiting pyroptosis

• Published in: Hepatology research Vol. 48; no. 3; pp. E194 - E202
• Main Authors: Wang, Jinglin, Ren, Haozhen, Yuan, Xianwen, Ma, Hucheng, Shi, Xiaolei, Ding, Yitao
• Format: Journal Article
• Language: English
• Published: Netherlands Wiley Subscription Services, Inc 01-02-2018
• Subjects: Alanine; Alanine transaminase; Ammonia; Apoptosis; Aspartate aminotransferase; Bilirubin; Cell death; Cytokines; D-Galactosamine; Data processing; Hepatocytes; Immunoregulation; Inflammation; Interleukin 10; Liver; liver disease; Liver failure; Mesenchymal stem cells; Mesenchyme; Pyroptosis; Ribonucleic acid; RNA; Skin & tissue grafts; Statistical analysis; stem cell; Stem cell transplantation; Stem cells; transplantation; pyroptosis; liver disease; stem cell; Immunoregulation; transplantation
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.12969

Aim
Recently, the benefit of mesenchymal stem cells (MSCs) as a cell‐based therapy for acute liver failure (ALF) has gained much attention, although the mechanism of action of MSCs in the treatment of ALF remains elusive. Pyroptosis is a novel form of programmed cell death with an intense inflammatory response. The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects through inhibiting pyroptosis in ALF.
Methods
Mesenchymal stem cells obtained from C57BL/6 mice were isolated and cultured according to an established protocol. The MSCs were transplanted into mice with D‐galactosamine (D‐Gal)‐induced ALF. Liver function, survival rate, histology, and inflammatory factors were determined. Exogenous recombinant rat interleukin (IL)‐10, ShIL‐RNA, and MCC950 (NLRP3 inhibitor) were given to the mice to explore the therapeutic mechanism of MSCs. Statistical analyses were carried out with spss version 19.0, and all data were analyzed by independent‐samples t‐test.
Results
Injection of IL‐10 or MSC transplantation ameliorated D‐Gal‐induced increase in alanine aminotransferase, aspartate aminotransferase, total bilirubin, NH3, and inflammatory cytokines. Blockage of IL‐10 confirmed the therapeutic significance of this cytokine.
Conclusion
Pyroptosis was inhibited after IL‐10 infusion and inhibition of NLRP3 by MCC950 reversed liver dysfunction.