Research Papers: Pathology:
IL-33 treatment attenuated diet-induced hepatic steatosis but aggravated hepatic fibrosis
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Yinjie Gao1,2, Yuan Liu1, Mei Yang1, Xiaodong Guo1, Min Zhang3, Hanwei Li3, Jin Li4 and Jingmin Zhao1
1 Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
2 Department of Infectious Diseases, Medical School of Chinese PLA, Beijing, China
3 Department of Liver Cirrhosis, Beijing 302 Hospital, Beijing, China
4 Department of Liver Transplantation and Research Center, Beijing 302 Hospital, Beijing, China
Jingmin Zhao, email:
Keywords: interleukin-33, high-fat diet, methionine-choline-deficient diet, steatosis, fibrosis, Pathology Section
Received: January 26, 2016 Accepted: April 26, 2016 Published: May 09, 2016
The aim of our work was to investigate the role of interleukin-33 (IL-33) and its receptor ST2 in the progression of diet-induced nonalcoholic steatohepatitis (NASH) in mice, and the characteristic expression in livers of patients with NASH. Mice were fed with high-fat diet (HFD) or methionine-choline 4-deficient diet (MCD) and injected intraperitoneally with IL-33. Both mRNA and protein expression levels of IL-33 and ST2 were up-regulated in the livers of mice fed with HFD or MCD. Treatment with IL-33 attenuated diet-induced hepatic steatosis and reduced activities of ALT in serum, as well as ameliorated HFD-induced systemic insulin resistance and glucose intolerance, while aggravated hepatic fibrosis in diet-induced NASH. Furthermore, treatment with IL-33 can also promote Th2 response and M2 macrophage activation and beneficial modulation on expression profiles of fatty acid metabolism genes in livers. ST2 deficiency did not affect hepatic steatosis and fibrosis when fed with controlling diet. IL-33 did not affect diet-induced hepatic steatosis and fibrosis in ST2 knockout mice. Meanwhile, in the livers of patients with NASH, IL-33 was mainly located in hepatic sinusoid, endothelial cells, and hepatic stellate cells. The mRNA expression level of IL-33 and ST2 was elevated with the progression of NASH. In conclusion, treatment with IL-33 attenuated diet-induced hepatic steatosis, but aggravated hepatic fibrosis, in a ST2-dependent manner.
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