Protective role and the mechanism of rapamycin against concanavalin A (ConA) induced autoimmune hepatitis in mice
10.3760/cma.j.issn.0254-5101.2016.01.009
- VernacularTitle:雷帕霉素减缓刀豆蛋白A诱导的自身免疫性肝炎及其机制
- Author:
Wenwen LI
;
Peng SUN
;
Weiqiang WANG
;
Wantong WU
;
Lu ZHOU
;
Bangmao WANG
;
Jie ZHANG
- Publication Type:Journal Article
- Keywords:
Rapamycin;
Dendritic cell;
Regulatory T cell;
Co-stimulatory molecule;
Autoimmune hepatitis
- From:
Chinese Journal of Microbiology and Immunology
2016;36(1):48-52
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effects of rapamycin (RAPA) on concanavalin A (ConA)-induced acute autoimmune hepatitis in a mouse model and to analyze the possible mechanism.Methods Thirty eight-week-old female C57BL/6 mice were randomly divided into three groups including control group,ConA model group and ConA + RAPA treatment group.The levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in serum samples were measured after injection of mice with ConA for 24 hours for assessing the liver function.Hematoxylin-eosin (HE) staining was used to observe the hepatic pathological changes in mice.Splenocytes were harvested 24 h after ConA injection for the detection of the percentages of splenic DCs,CD4+T,CD8+T and CD4+ Foxp3+ Treg cells as well as the expression of co-stimulatory molecules (CD40,CD80 and CD86) on DCs by using flow cytometry.Results The levels of ALT and AST in mice from the RAPA treatment group were significantly lower than those of the ConA model group.Results of the HE staining assay showed that the liver damages in RAPA treated mice were less severe than those in mice from the ConA model group.Compared with mice form the ConA model group,those treated with RAPA showed decreased percentages of splenic CD4+ and CD8+ T cells,inhibited expression of CD80 and CD86 on splenic DCs,but increased percentages of splenic CD4+ Foxp3+ Treg cells.No statistically significant differences in the percentages of splenic DCs and the expression of CD40 were observed between the RAPA treatment group and the ConA model group.Conclusion The immunosuppressive effects of RAPA on mice with ConA-induced hepatitis might be achieved through the regulation of immune cells including DCs and T cells in spleen tissues.This study might pave the way for further investigation on the prevention and treatment of autoimmune hepatitis.
