1α,25‐dihydroxyvitamin D3 inhibits anti‐CD40 plus IL‐4‐mediated IgE production in vitro
1α,25‐dihydroxyvitamin D3 inhibits anti‐CD40 plus IL‐4‐mediated IgE production in vitro
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DOI：
10.1002/1521-4141(200212)32:12
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发表时间：
2002-12
影响因子：
5.4
通讯作者：
G. Heine;K. Anton;B. Henz;M. Worm
中科院分区：
文献类型：
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作者：
G. Heine;K. Anton;B. Henz;M. Worm
在本研究中，我们检测了来自健康供体的B细胞中抗CD40+IL - 4介导的B细胞增殖和免疫球蛋白合成是否受到维生素D （VD）及其低高钙类似物EB1089的影响。维生素D受体（VDR）表达分析显示，只有抗CD40+IL - 4刺激的B细胞表达VDR，而静止的B细胞不表达VDR。对B细胞增殖的研究表明，抗CD40+IL - 4介导的B细胞增殖不受VD或EB1089的影响。相比之下，VD和EB1089对IgE合成均有明显抑制作用，VD和EB1089分别在10-10 M和10-12 M浓度下抑制IgE合成，在10-6 M浓度下抑制最大（VD为85.5±9.7%，EB1089为77.3±10.8%）。抗CD40+IL - 4刺激后，VD未显著抑制其他Ig （IgA和IgG）的产生，IgM的产生仅轻微降低（18.7±7.9%）。这些观察结果在抗CD40+IL - 4刺激后的B细胞内不同同种型染色中得到证实，显示出VD存在时IgE+细胞的强烈减少。对已知影响IgE产生的分子（CD23和IL - 6）的分析表明，这些分子不参与VD依赖性的IgE产生抑制。相反，VD抑制epsilon生殖系转录（41.2±26.1%;n=5），刺激细胞中NF - κB （p50和p65）蛋白表达也受到抑制。这些数据表明，VD及其类似物EB1089在体外抑制抗CD40+IL - 4刺激的B细胞产生IgE。涉及的机制包括epsilon生殖系转录、NF - κB激活和开关重组，这表明在抗CD40+IL - 4刺激的B细胞中VD作用的复杂机制是负责的。
In the present study, we examined whether anti‐CD40+IL‐4‐mediated B cell proliferation and immunoglobulin synthesis is affected by vitamin D (VD) and its low‐hypercalcemic analogue EB1089 in Bcells from healthy donors. Analysis of vitamin D receptor (VDR) expression showed that only anti‐CD40+IL‐4‐stimulated, but not resting B cells express VDR. Studies on B cell proliferation revealed that anti‐CD40+IL‐4‐mediated proliferation of B cells was not affected by VD or EB1089. By contrast, IgE synthesis was markedly inhibited by both, VD and EB1089, starting at concentrations from 10–10 M for VD and 10–12 M for EB1089, with maximal inhibition at 10–6 M (VD 85.5±9.7%; EB1089 77.3±10.8%). The production of the other Ig (IgA and IgG) was not significantly inhibited by VD after anti‐CD40+IL‐4 stimulation, and IgM production was only slightly reduced (18.7±7.9%). These observations were confirmed by intracellular staining of the different isotypes in B cells after anti‐CD40+IL‐4 stimulation, which showed a strong reduction of IgE+ cells in the presence of VD. Analyses of molecules that are known to affect IgE production (CD23 and IL‐6) revealed that these are not involved in VD‐dependent inhibition of IgE production. By contrast, epsilon germ‐line transcription was inhibited by VD (41.2±26.1%; n=5), as was NF‐κB (p50 and p65) protein expression in stimulated cells. These data show that VD and its analogue EB1089 inhibit IgE production of anti‐CD40+IL‐4‐stimulated B cells in vitro. Theinvolved mechanism includes epsilon germ‐line transcription, NF‐κB activation and switch recombination suggesting that complex mechanisms of VD action in anti‐CD40+IL‐4‐stimulated B cells areresponsible.