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胃肠道过敏小鼠模型中羊奶 αS1-酪蛋白诱导的过敏反应。

Allergic responses induced by goat milk αS1-casein in a murine model of gastrointestinal atopy.

机构信息

AgResearch Ruakura, Hamilton, New Zealand.

出版信息

J Dairy Sci. 2012 Jan;95(1):83-90. doi: 10.3168/jds.2011-4829.

Abstract

Up to 3% of young children develop milk allergy and this may influence the development of immune-mediated diseases in later life. One protein that has been associated with allergic reactions to ruminant milk is α(S1)-casein (CN). Studies suggest that goat milk with low levels of α(S1)-CN may reduce allergenicity of milk, but the dose response to α(S1)-CN has not been confirmed. In this study, we examined the immune response to varying levels of goat α(S1)-CN in a mouse model of gastrointestinal allergy. BALB/c mice (aged 5 wk) were given intraperitoneal injections with α(S1)-CN and aluminum as adjuvant at 1 and 3 wk to sensitize mice to the antigen. In wk 5, groups of fasting mice (n=8/group) were challenged 4 times on alternate days by intragastric gavage with saline or 2, 10, or 20mg of α(S1)-CN. Serum levels of specific IgE, IgG(1), and IgG(2a) antibodies and mouse mast cell protease-I were determined. Interleukin-4, IL-10, and IFN-γ responses to 48-h activation with antigen were measured in cultured splenocytes. We determined that mice sensitized with α(S1)-CN had higher titers of specific IgG(1) and IgE antibodies compared with controls; however, groups challenged with differing doses of α(S1)-CN did not differ. The group challenged with the highest dose of α(S1)-CN had a 10-fold increase in mouse mast cell protease-I compared with the group challenged with saline. Both IL-4 and IL-10 were produced in a dose-dependent manner by cultured splenocytes incubated with α(S1)-CN. Overall, α(S1)-CN stimulated the production of cytokines associated with allergic disease in a dose-dependent manner. Thus, milk with lower levels of α(S1)-CN should contribute to a lesser antigenic burden.

摘要

高达 3%的幼儿会发展成牛奶过敏,这可能会影响他们日后免疫介导性疾病的发生。一种与反刍动物奶的过敏反应有关的蛋白质是α(S1)-酪蛋白(CN)。研究表明,低水平α(S1)-CN 的山羊奶可能会降低奶的致敏性,但α(S1)-CN 的剂量反应尚未得到证实。在这项研究中,我们在胃肠道过敏的小鼠模型中检查了对不同水平的山羊α(S1)-CN 的免疫反应。5 周龄的 BALB/c 小鼠(5 周龄)在第 1 周和第 3 周接受α(S1)-CN 和铝作为佐剂的腹腔内注射,以使小鼠对该抗原致敏。在第 5 周,禁食的小鼠(每组 8 只)在 4 天内通过胃内灌胃接受盐水或 2、10 或 20mgα(S1)-CN 的 4 次挑战。测定血清特异性 IgE、IgG(1)和 IgG(2a)抗体和小鼠肥大细胞蛋白酶-I 的水平。在培养的脾细胞中,通过 48 小时抗原激活来测量白细胞介素-4、IL-10 和 IFN-γ 反应。我们发现,用α(S1)-CN 致敏的小鼠与对照组相比,具有更高滴度的特异性 IgG(1)和 IgE 抗体;然而,用不同剂量的α(S1)-CN 进行挑战的组没有差异。用最高剂量α(S1)-CN 进行挑战的组与用盐水进行挑战的组相比,小鼠肥大细胞蛋白酶-I 增加了 10 倍。用α(S1)-CN 孵育的培养脾细胞以剂量依赖性方式产生白细胞介素-4 和白细胞介素-10。总的来说,α(S1)-CN 以剂量依赖性方式刺激与过敏疾病相关的细胞因子的产生。因此,低水平α(S1)-CN 的牛奶应该会导致较小的抗原负担。

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