Adipose tissue-derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL-17-mediated inflammation
| Autor: | Hatsune Mochida, Masayuki Takamura, Keiko Yoshida, Kousuke Ishida, Masatoshi Yamato, Ho Thuy Bich Tuyen, Taro Yamashita, Shuichi Kaneko, Takashi Wada, Tatsuya Yamashita, Takuya Komura, Eishiro Mizukoshi, Yoshio Sakai, Masao Honda, Alessandro Nasti, Soichiro Usui, Akihiro Seki, Kazunori Kawaguchi |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_treatment
Adipose tissue Inflammation Diet High-Fat Liver Cirrhosis Experimental digestive system Cell Line Fibrosis Non-alcoholic Fatty Liver Disease Hepatic Stellate Cells Medicine Animals Cell Proliferation Hepatology business.industry Stem Cells Interleukin-17 Gastroenterology nutritional and metabolic diseases medicine.disease digestive system diseases Coculture Techniques Mice Inbred C57BL Cytokine Adipose Tissue Liver Hepatic stellate cell Cancer research Disease Progression Female medicine.symptom Steatohepatitis Stem cell Inflammation Mediators business Hepatic fibrosis Stem Cell Transplantation |
| Zdroj: | Journal of gastroenterology and hepatologyReferences. 34(8) |
| ISSN: | 1440-1746 |
| Popis: | Background and aim The pathological features of non-alcoholic steatohepatitis (NASH) have not been determined, so fundamental treatment has not been established. Adipose-tissue-derived stromal/stem cells (ADSCs) are beneficial for repair/regenerative therapy of impaired organs because of their immuno-modulatory capability. In this study, we assessed how liver damage progresses during the early development phase of the murine NASH model and investigated whether ADSCs are preventatively efficacious against the fibrosis progression of NASH. Methods C57BL/6J mice were fed with atherogenic high fat or high-fat diet 60 developing into NASH or simple steatosis. Their hepatic inflammatory cells (HICs) were analyzed by cDNA microarray. NASH mice were treated with ADSCs injected into spleen when hepatic inflammation was initially observed, and liver samples were analyzed. The effect of ADSCs on the mice hepatic stellate cell (HSC) line stimulated by recombinant IL-17 and HICs from NASH mice was analyzed. Results The gene expression features of HICs implicated as humoral cytokine mediators of lymphoid cells during NASH development, compared with a simple steatosis model. One of the featured cytokines was IL-17. The development of hepatic fibrosis was alleviated when NASH mice were treated with ADSCs as well as treated with anti-IL-17 antibody, and the frequency of IL-17-secreting HICs decreased. NASH-HICs enhanced proliferation of HSCs, in which proliferation was sensitive to IL-17 stimulation. The stimulatory effect of NASH-HICs on the activation of HSCs was attenuated by co-culture with ADSCs. Conclusion ADSCs treatment prevented progression of NASH fibrosis by suppressing IL-17-mediated inflammation, which was associated with HSCs activation. |
| Databáze: | OpenAIRE |
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