Chemical chaperone TUDCA selectively inhibits production of allergen-specific IgE in a low-dose model of allergy.

Q3 Biochemistry, Genetics and Molecular Biology
D B Chudakov, O A Shustova, O D Kotsareva, A A Generalov, M S Streltsova, Yu D Vavilova, G V Fattakhova
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引用次数: 0

Abstract

The cellular response to endoplasmic reticulum (ER) stress accompanies plasma cell maturation and is one of triggers and cofactors of the local inflammatory response. Chemical chaperones, low-molecular substances that eliminate pathological ER stress, are proposed as means of treating pathologies associated with ER stress. The aim of this study was to evaluate the effect and mechanisms of influence of chemical chaperones on the humoral response in a low-dose model of allergy. The allergic immune response was induced in BALB/c mice by repeated administration of ovalbumin at a dose of 100 ng for 6 weeks. Some animals were injected with both the antigen and the chemical chaperones, TUDCA (tauroursodeoxycholic acid) or 4-PBA (4-phenylbutyrate). Administration of TUDCA, but not 4-PBA, suppressed production of allergen-specific IgE (a 2.5-fold decrease in titer). None of the chemical chaperones affected the production of specific IgG1. The effect of TUDCA was associated with suppression of the switch to IgE synthesis in regional lymph nodes. This phenomenon was associated with suppressed expression of genes encoding cytokines involved in type 2 immune response, especially Il4 and Il9, which in turn could be caused by suppression of IL-33 release. In addition, TUDCA significantly suppressed expression of the cytokine APRIL, and to a lesser extent, BAFF. Thus, TUDCA inhibition of the allergy-specific IgE production is due to suppression of the release of IL-33 and a decrease in the production of type 2 immune response cytokines, as well as suppression of the expression of the cytokines APRIL and BAFF.

在低剂量过敏模型中,化学伴侣 TUDCA 可选择性地抑制过敏原特异性 IgE 的产生。
细胞对内质网(ER)应激的反应伴随着浆细胞的成熟,是局部炎症反应的诱因和辅助因子之一。化学伴侣是一种能消除病理性内质网应激的低分子物质,被认为是治疗与内质网应激有关的病症的手段。本研究旨在评估化学伴侣在低剂量过敏模型中对体液反应的影响及其机制。通过在 BALB/c 小鼠体内连续 6 周重复注射 100 纳克剂量的卵清蛋白来诱导过敏性免疫反应。有些动物同时注射了抗原和化学合剂 TUDCA(牛磺酸去氧胆酸)或 4-PBA(4-苯基丁酸)。注射 TUDCA 可抑制过敏原特异性 IgE 的产生(滴度下降 2.5 倍),而注射 4-PBA 则不会。所有化学伴侣都不会影响特异性 IgG1 的产生。TUDCA 的作用与抑制区域淋巴结中 IgE 合成的转换有关。这种现象与编码参与 2 型免疫反应的细胞因子(尤其是 Il4 和 Il9)的基因表达受到抑制有关,而抑制 IL-33 的释放又可能导致这种现象。此外,TUDCA 还显著抑制了细胞因子 APRIL 的表达,并在较小程度上抑制了 BAFF 的表达。因此,TUDCA 抑制过敏特异性 IgE 的产生是由于抑制了 IL-33 的释放,减少了 2 型免疫反应细胞因子的产生,以及抑制了细胞因子 APRIL 和 BAFF 的表达。
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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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