Reichel H, Koeffler H P, Tobler A, Norman A W
Proc Natl Acad Sci U S A. 1987 May;84(10):3385-9. doi: 10.1073/pnas.84.10.3385.
1 alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D3, inhibited synthesis of gamma-interferon (IFN-gamma) by phytohemagglutinin-activated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-gamma protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)2D3 concentration (0.1 nM). 1,25-(OH)2D3 also inhibited accumulation of IFN-gamma mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)2D3 to modulate IFN-gamma protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-gamma synthesis by PBLs was specific for 1,25-(OH)2D3; the potencies of other vitamin D3 metabolites were correlated with their affinities for the cellular 1,25-(OH)2D3 receptor. The time course of 1,25-(OH)2D3 receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)2D3-mediated inhibition of IFN-gamma synthesis. In selected experiments, T-lymphocyte-enriched cell preparations were utilized. In these experiments, 1,25-(OH)2D3 was equally active as in PBL preparations. Finally, we examined the effects of 1,25-(OH)2D3 on the constitutive IFN-gamma production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-gamma synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)2D3, whereas IFN-gamma synthesis by Ab-VDR cells was not altered by 1,25-(OH)2D3. The data presented in this study provide further evidence for a role of 1,25-(OH)2D3 in immunoregulation.
1α,25 - 二羟维生素D3 [1,25 - (OH)2D3]，维生素D3的生物活性代谢产物，可抑制植物血凝素激活的外周血淋巴细胞（PBLs）合成γ - 干扰素（IFN - γ）。生理浓度的1,25 - (OH)2D3（0.1 nM）可使PBL培养基中IFN - γ蛋白水平显著降低。1,25 - (OH)2D3还以剂量依赖的方式抑制活化的PBLs中IFN - γ mRNA的积累。在高浓度重组人白细胞介素2存在的情况下，1,25 - (OH)2D3调节IFN - γ蛋白合成的能力未改变。PBLs对IFN - γ合成的抑制作用对1,25 - (OH)2D3具有特异性；其他维生素D3代谢产物的效力与其对细胞1,25 - (OH)2D3受体的亲和力相关。植物血凝素激活的PBLs中1,25 - (OH)2D3受体表达的时间进程与1,25 - (OH)2D3介导的IFN - γ合成抑制的时间进程相关。在选定的实验中，使用了富含T淋巴细胞的细胞制剂。在这些实验中，1,25 - (OH)2D3的活性与在PBL制剂中相同。最后，我们研究了1,25 - (OH)2D3对由I型人嗜T淋巴细胞病毒转化的两个人T淋巴细胞系组成型IFN - γ产生的影响。这些细胞系分别来自一名正常供体（细胞系S - LB1）和一名患有2型维生素D依赖性佝偻病的患者（细胞系Ab - VDR）。1,25 - (OH)2D3以剂量依赖的方式抑制S - LB1细胞的IFN - γ合成，而1,25 - (OH)2D3对Ab - VDR细胞的IFN - γ合成无影响。本研究提供的数据进一步证明了1,25 - (OH)2D3在免疫调节中的作用。
