1,25(OH)(2)D(3) Protects Liver Fibrosis Through Decreasing the Generation of TH17 Cells

BACKGROUND: The aim of this study was to study the effects of 1-alpha,25-dihydroxy-cholecalcifero (1,25(OH)(2)D(3)) on liver fibrosis and the generation of Th17 cells in vivo and in vitro. MATERIAL/METHODS: Thirty C57 mice were randomly divided into control, model, and treatment groups. Hepatic fibrosis was induced by subcutaneous injection of CCl4. Liver fibrosis condition was evaluated through pathological inspection and blood biochemical examination of liver function. Immunohistochemical assays were used to detect the expression of α-SMA, TGF-β, and collagen I to observe hepatic stellate cell activation level. Flow cytometry, ELISA, and RT-PCR were performed to explore the association between 1,25(OH)(2)D(3) and Th17 cell differentiation. RESULTS: Collagen I, TGF-β, and α-SMA were decreased after 1,25(OH)(2)D(3) treatment. Consistently, RORγt mRNA and the rate of Th17 cells was significantly reduced after 1,25(OH)(2)D(3) treatment. In vitro, the proportion of Th17 cells was also obviously reduced in the 1,25(OH)(2)D(3) group, and mRNA levels of IL-17A, IL-22, RORγt, and RORα were significantly decrease in the 1,25(OH)(2)D(3) group compared to the control group. CONCLUSIONS: Treatment with 1,25(OH)(2)D(3) can alleviate the damage caused by liver fibrosis. Experiments in vivo and in vitro showed that 1,25(OH)(2)D(3) treatment deceased the rates of Th1 and Th17 cells and increased the rate of Th2 cells. The level of IL-17A, IL-22 and IFN-γ were decreased, while the level of IL-4 was increased by the treatment of 1,25(OH)(2)D(3).