Peña-Juárez Ma Concepción, Campos-Rodríguez Rafael, Godínez-Victoria Marycarmen, Cruz-Hernández Teresita Rocío, Reyna-Garfias Humberto, Barbosa-Cabrera Reyna Elizabeth, Drago-Serrano Maria Elisa
a Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina , Instituto Politécnico Nacional , México DF , México.
b Departamento de Sistemas Biológicos , Universidad Autónoma Metropolitana, Unidad Xochimilco , México DF , México.
Immunol Invest. 2016 Oct;45(7):652-67. doi: 10.1080/08820139.2016.1202959. Epub 2016 Sep 9.
Secretory IgA (SIgA) has a pivotal role in gut homeostasis, which can be disturbed by stress. SIgA is formed by IgA-dimers (associated by the J-chain) and the secretory component, a protein derivative of polymeric immunoglobulin receptor (pIgR). Given the gut immuno-modulatory properties of bovine lactoferrin (bLf), the aim of this study was to compare, after bLf treatment followed by acute stress, the IgA response and IgA-associated parameters in proximal versus distal small intestine. Male BALB/c mice (n = 6) were orally treated with bLf (50, 500, and 5000 μg) for 7 days, then stressed by immobilization for 1 h, and sacrificed. In proximal and distal segments, levels were determined of IgA in gut secretions (enzyme-linked immunosorbent assay [ELISA]), the α-/J-chain and pIgR proteins in epithelial cells (Western-blot), and mRNA expression of the α-/J-chain, pIgR, and interleukins (ILs) in mucosa (RT-PCR). Data were compared by two-way analysis of variance (ANOVA) (significance at P < 0.05). Under acute stress, bLf triggered higher levels of IgA, SIgA, and anti-bLf-IgA as well as greater mRNA expression of pIgR, IL-4, and IL-6 (500 µg) in proximal intestine, while inducing higher levels of the total IgA, α-/J-chain, and pIgR proteins as well as greater mRNA expression of the α-chain and IL-4 (5000 µg) in distal intestine. Compared to unstressed/bLf-untreated mice, plasma corticosterone (a stress biomarker, measured by ELISA) increased in stressed/bLf-treated (0, 50 and 500 µg) and unstressed/bLf-treated (5000 µg) mice. The interplay of corticosterone with gut neuroendocrine factors may have elicited signals creating anti-inflammatory conditions for an IgA-response profile in each intestinal region, according to the bLf concentration administered.
分泌型免疫球蛋白A(SIgA)在肠道内环境稳态中起关键作用,而这种内环境稳态可能会受到应激的干扰。SIgA由IgA二聚体(通过J链相连)和分泌成分组成,分泌成分是多聚免疫球蛋白受体(pIgR)的一种蛋白质衍生物。鉴于牛乳铁蛋白(bLf)具有肠道免疫调节特性,本研究的目的是比较在bLf处理后再施加急性应激的情况下,近端小肠与远端小肠中IgA反应及与IgA相关的参数。雄性BALB/c小鼠(n = 6)口服bLf(50、500和5000微克)7天,然后进行1小时的固定应激,随后处死。在近端和远端肠段,测定肠道分泌物中IgA的水平(酶联免疫吸附测定[ELISA])、上皮细胞中α链/J链和pIgR蛋白的水平(蛋白质免疫印迹法)以及黏膜中α链/J链、pIgR和白细胞介素(ILs)的mRNA表达水平(逆转录聚合酶链反应[RT-PCR])。数据通过双向方差分析(ANOVA)进行比较(P < 0.05时有统计学意义)。在急性应激情况下,bLf在近端小肠中引发了更高水平的IgA、SIgA和抗bLf-IgA,以及pIgR、IL-4和IL-6(500微克)更高的mRNA表达,而在远端小肠中诱导了更高水平的总IgA、α链/J链和pIgR蛋白,以及α链和IL-4(5000微克)更高的mRNA表达。与未应激/未用bLf处理的小鼠相比,血浆皮质酮(一种应激生物标志物,通过ELISA测定)在应激/用bLf处理(0、50和500微克)以及未应激/用bLf处理(5000微克)的小鼠中有所升高。根据所施用的bLf浓度,皮质酮与肠道神经内分泌因子的相互作用可能引发了信号,为每个肠道区域的IgA反应谱创造了抗炎条件。