Preventive effects of 1,25-（OH）2VD3 against ConAinduced mouse hepatitis through promoting vitamin D receptor gene expression

Preventive effects of 1,25-(OH)2VD3 against ConA-induced mouse hepatitis through promoting vitamin D receptor gene expression

Aim:

To investigate the immunosuppressive effects of 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂VD₃) on concanavalin A (ConA)-induced hepatitis and elucidate the action mechanism.

Methods:

Female BALB/C mice were intravenously administered ConA (20 mg/kg) to induce acute immunological liver injury. Liver damage was evaluated in respect to serum alanine transaminase (ALT) level and liver histological changes. The proliferation of splenocytes was measured by using [³H]-thymidine incorporation. The cytokine level in the cultured splenocyte supernatant was determined by using enzyme-linked immunosorbent assays (ELISAs). The percentage of different splenic T cell subtypes was analyzed by using flow cytometry. The expression of splenic vitamin D receptor (VDR) mRNA and protein was detected by using real-time qRT-PCR and Western blot, respectively.

Results:

1,25-(OH)₂VD₃ (2.5 μg/kg, ip) significantly decreased the serum ALT levels and markedly attenuated the histological liver damage. The beneficial effect of 1,25-(OH)₂VD₃ was associated with: (i) inhibition of CD4⁺ T cell activation; (ii) reduction of interferon-γ (IFN-γ) and elevation of both IL-4 and IL-5 in supernatants of cultured splenocytes; and (iii) elimination of activated T cells by increasing VDR mRNA and protein expression in the spleen.

Conclusion:

1,25-(OH)₂VD₃ had a significant protective effect against ConA-induced hepatitis, and its mechanism of action was associated with down-regulation of T cell-mediated immunity and up-regulation of VDR gene expression.