Premium
Interleukin‐10 secreted by mesenchymal stem cells attenuates acute liver failure through inhibiting pyroptosis
Author(s) -
Wang Jinglin,
Ren Haozhen,
Yuan Xianwen,
Ma Hucheng,
Shi Xiaolei,
Ding Yitao
Publication year - 2018
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12969
Subject(s) - mesenchymal stem cell , pyroptosis , medicine , transplantation , interleukin , pharmacology , cytokine , proinflammatory cytokine , inflammation , cancer research , immunology , pathology , inflammasome
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.