Retinoic acid inhibits CD40 + interleukin-4-mediated IgE production in vitro.
Retinoic acid inhibits CD40 + interleukin-4-mediated IgE production in vitro.
复制标题
视黄酸在体外抑制 CD40 白细胞介素 4 介导的 IgE 产生。
作者：
M. Worm;J. Krah;R. A. Manz;B. Henz
为阐明维甲酸（RA）在抗CD 40+白细胞介素4（IL-4）介导的B细胞活化中的作用，研究了10（-12）~ 10（-6）mol/L RA对抗CD 40（1 μ g/mL）+ IL-4（5 ng/mL）介导的健康人外周血单个核细胞（PBMC）和B细胞增殖和IG合成的影响。RA以剂量依赖性方式抑制抗CD 40 + IL-4介导的PBMC和B细胞增殖，全反式RA对PBMC和B细胞的最大抑制率分别为62% +/- 5%和55% +/- 4.4%，13-顺式RA分别为58% +/- 6.7%和51% +/-4.7%。当RA对B细胞和PBMC的浓度分别为>10（-14）mol/L和>10（-10）mol/L时，IgE合成的抑制作用更明显。对于全反式RA（94% +/- 1.8%）和13-顺式RA（96% +/- 3.2%），在10（-8）mol/L时对B细胞IgE产生的最大抑制作用。低浓度的RA抑制IgE合成（10（-10）mol/L）既不影响B细胞增殖，也不影响伊加、IgG和IgM的产生。在这种抑制IgE的产生所涉及的机制的阐明表明，RA的生殖细胞转录减少，而产生的干扰素-γ（IFN-γ）的RA的存在下没有增强。为了区分RA效应是否由RA受体α、β和γ介导，通过逆转录酶-聚合酶链反应（RT-PCR）检测维甲酸受体（RAR）的表达。数据显示未刺激的人外周B细胞表达RA受体α、β和γ的mRNA。使用具有不同受体结合特异性的类维生素A（CD 336、CD 437、CD 2019、CD 367），所有四种衍生物均显示出IgE合成的剂量依赖性抑制，但最显著的是RA以高特异性结合α受体。综上所述，本研究表明，RA抑制体外抗CD 40 + IL-4刺激的B细胞的IgE产生。
To elucidate the role of retinoic acid (RA) in anti-CD40 + interleukin-4 (IL-4)-mediated B-cell activation, the effect of 10(-12) to 10(-6) mol/L RA was studied in anti-CD40 (1 microgram/mL) + IL-4 (5 ng/mL)-mediated proliferation and Ig synthesis by human peripheral blood mononuclear cells (PBMC) and B cells in healthy donors. Anti-CD40 + IL-4-mediated proliferation of PBMC and B cells was inhibited by RA in a dose-dependent manner, with maximal inhibition of 62% +/- 5% in PBMC and 55% +/- 4.4% in B cells by all-trans RA, and 58% +/- 6.7% and 51% +/- 4.7%, respectively by 13-cis RA. IgE synthesis was even more markedly inhibited by RA starting at concentrations of >10(-14) mol/L for B cells and >10(-10) mol/L for PBMC. Maximal inhibition of IgE production for B cells was at 10(-8) mol/L for all-trans RA (94% +/- 1.8%) and 96% +/- 3.2% for 13-cis RA. Low concentrations of RA inhibiting IgE synthesis (10(-10) mol/L) affected neither B-cell proliferation nor the production of IgA, IgG, and IgM. Elucidation of the mechanism involved in this inhibition of IgE production shows that epsilon germline transcription is decreased by RA, whereas production of interferon-gamma (IFN-gamma) was not enhanced in the presence of RA. To differentiate whether the RA effect was mediated by RA receptors alpha, beta, and gamma, the expression of the retinoic acid receptors (RAR) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The data show that unstimulated human peripheral B cells express mRNA of the RA receptor alpha, beta, and gamma. Using retinoids with different receptor binding specificity (CD336, CD437, CD2019, CD367), dose-dependent inhibition of IgE synthesis was shown by all four derivates, but was most marked by an RA binding the alpha receptor with high specificity. Taken together, this study shows that RA inhibits IgE production of anti-CD40 + IL-4-stimulated B cells in vitro.
影响因子：
158.5
作者：
GOODMAN, DS
通讯作者：
GOODMAN, DS