Effect of β-alanine on humoral immune response in low-dose allergy model

D. Chudakov, O. Kotsareva, D. S. Tsaregorotseva, E. Kashirina, G. Fattakhova
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Abstract

At the present time, the efforts of many research groups around the world are aimed at finding new factors triggering the allergic sensitization process linked with IgE synthesis to harmless allergens. According to the recent data, production of tissue cytokines is induced in tissue cells by alarmins, thus, in turn, eliciting pro-allergic immune response. Previously we have shown that β-alanine could be a potential alarmin capable to stimulate production of tissue cytokines. The aim of this work was to determine the impact of β-alanine on humoral immune response in low-dose allergy model. BALB/c mice were immunized by recombinant Asp f 2 protein or commercial ovalbumin (OVA) in the withers 3 times a week with or without β-alanine supplementation. To determine the mechanism of β-alanine effect, α-L-alanine, an isomer which is not MrgD receptor ligand, and β-aminoisobutyrate with β-alanine-like affinity to MrgD ligand, were compared. According to our data, β-alanine stimulated specific IgE and IgG1 production in a short-term course (7 immunizations) and enhanced antibody affinity after long-term (14 immunizations) protocol in the case of low-immunogenic protein Asp f 2. In the case of high-immunogenic OVA protein, the impact of β-alanine was significant only upon antibody affinity. Hence, β-alanine accelerates specific IgE production in the case of low-immunogenic protein. The impact of β-alanine on specific IgE production was not linked to specific MrgD receptor activation, because β-aminoisobutyrate, which is the other ligand of this receptor, did not have a similar effect upon humoral immune response. The effect of β-alanine on IgG1 production seems also independent of MrgD receptor, since the common proteinogenic amino acid α-L-alanine also enhanced specific IgG1 production. The effect of β-alanine on humoral immune response could be linked to its non-specific action, e.g., due to its ability to induce oxidative stress through blocking taurine transporter, or due to its ability to stimulate cellular metabolism.
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β-丙氨酸对低剂量变态反应模型体液免疫反应的影响
目前,世界各地许多研究小组的努力旨在寻找与IgE合成相关的过敏致敏过程的新因素,以对抗无害的过敏原。根据最近的数据,危言耸听在组织细胞中诱导组织细胞因子的产生,从而引发促过敏免疫反应。以前我们已经证明,β-丙氨酸可能是一种潜在的危言耸听蛋白,能够刺激组织细胞因子的产生。本工作的目的是确定β-丙氨酸对低剂量变态反应模型中体液免疫反应的影响。用重组Asp f2蛋白或商品卵清蛋白(OVA)免疫BALB/c小鼠,每周3次,添加或不添加β-丙氨酸。为了确定β-丙氨酸效应的机制,比较了非MrgD受体配体的异构体α-L-丙氨酸和对MrgD配体具有β-丙氨酸样亲和力的β-氨基异丁酸。根据我们的数据,在低免疫原性蛋白Asp f 2的情况下,β-丙氨酸在短期内(7次免疫)刺激特异性IgE和IgG1的产生,并在长期(14次免疫)方案后增强抗体亲和力。在高免疫原性OVA蛋白的情况下,β-丙氨酸的影响仅对抗体亲和力显著。因此,在低免疫原性蛋白质的情况下,β-丙氨酸加速特异性IgE的产生。β-丙氨酸对特异性IgE产生的影响与特异性MrgD受体的激活无关,因为该受体的另一个配体β-氨基异丁酸对体液免疫反应没有类似的影响。β-丙氨酸对IgG1产生的影响似乎也与MrgD受体无关,因为常见的蛋白质生成氨基酸α-L-丙氨酸也增强了特异性IgG1的产生。β-丙氨酸对体液免疫反应的影响可能与其非特异性作用有关,例如,由于其通过阻断牛磺酸转运蛋白诱导氧化应激的能力,或由于其刺激细胞代谢的能力。
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