Key Laboratory of Liver and Kidney Diseases of Education Ministry, Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai, China.
Acta Pharmacol Sin. 2010 Jun;31(6):703-8. doi: 10.1038/aps.2010.53.
To investigate the immunosuppressive effects of 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)VD(3)) on concanavalin A (ConA)-induced hepatitis and elucidate the action mechanism.
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 [(3)H]-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.
1,25-(OH)(2)VD(3) (2.5 microg/kg, ip) significantly decreased the serum ALT levels and markedly attenuated the histological liver damage. The beneficial effect of 1,25-(OH)(2)VD(3) was associated with: (i) inhibition of CD4(+) T cell activation; (ii) reduction of interferon-gamma (IFN-gamma) 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.
1,25-(OH)(2)VD(3) 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.
研究 1,25-二羟维生素 D(3)（1,25-(OH)(2)VD(3)）对刀豆蛋白 A（ConA）诱导的肝炎的免疫抑制作用，并阐明其作用机制。
雌性 BALB/C 小鼠静脉注射 ConA（20mg/kg）诱导急性免疫性肝损伤。通过血清丙氨酸转氨酶（ALT）水平和肝组织学变化评估肝损伤。用[3H]-胸苷掺入法检测脾淋巴细胞增殖。用酶联免疫吸附试验（ELISA）检测培养脾细胞上清液中的细胞因子水平。用流式细胞术分析脾不同 T 细胞亚群的比例。用实时 qRT-PCR 和 Western blot 分别检测脾维生素 D 受体（VDR）mRNA 和蛋白的表达。
1,25-(OH)(2)VD(3)（2.5μg/kg，ip）显著降低血清 ALT 水平，并明显减轻肝组织学损伤。1,25-(OH)(2)VD(3)的有益作用与：（i）抑制 CD4+T 细胞活化；（ii）减少干扰素-γ（IFN-γ）和增加白细胞介素-4（IL-4）和白细胞介素-5（IL-5）在培养脾细胞上清液中的表达；和（iii）通过增加脾中 VDR mRNA 和蛋白表达消除活化的 T 细胞。
1,25-(OH)(2)VD(3)对 ConA 诱导的肝炎具有显著的保护作用，其作用机制与下调 T 细胞介导的免疫和上调 VDR 基因表达有关。
