首页> 美国卫生研究院文献>Bosnian Journal of Basic Medical Sciences >Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29
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Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29

机译:从人母乳中分离的三叶因子3下调肠上皮细胞HT-29中的细胞因子(IL8和IL6)并促进人β防御素(hBD2和hBD4)的表达

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摘要

Trefoil factors (TFF) are secretory products of mucin producing cells. They play a key role in the maintenance of the surface integrity of oral mucosa and enhance healing of the gastrointestinal mucosa by a process called restitution. TFF comprises the gastric peptides (TFF1), spasmolytic peptide (TFF2), and the intestinal trefoil factor (TFF3). They have an important and necessary role in epithelial restitution within the gastrointestinal tract. Significant amounts of TFF are present in human milk. This study aimed to determine a possible correlation between TFF3 isolated from human breast milk and levels of cytokines (IL8 and IL6) and defensins (hBD2 and hBD4) in intestinal epithelial cells HT-29 treated with trefoil. Samples of human milk were collected within 2-4 weeks postpartum from healthy human mothers (18-30-years-old) by manual breast massage, and TFF3 was purified by ammonium sulfate precipitation, isoelectric precipitation, DEAE-chromatography, and gel filtration. In this work we measured the concentrations and mRNA levels of cytokines and defensins by immunoassay (ELISA) and semiquantitative RT-PCR technique, respectively. Also we measured the peroxidase activity. We present the first evidence of human milk TFF3 purification. Here we show that the presence of TFF3 isolated from milk strongly correlates with downregulation of IL8 and IL6 in human intestinal epithelial cells. On the other hand, TFF3 activated the epithelial cells in culture to produce beta defensins 2 (hBD2) and beta defensins 4 (hBD4). These findings suggest that TFF can activate intestinal epithelial cells and could actively participate in the immune system of breastfed babies by inducing the production of peptides related to innate defence, such as defensins.
机译:三叶因子(TFF)是产生粘蛋白的细胞的分泌产物。它们在维持口腔粘膜表面完整性和通过称为复原的过程增强胃肠道粘膜愈合中起关键作用。 TFF包括胃肽(TFF1),解痉肽(TFF2)和肠三叶因子(TFF3)。它们在胃肠道内的上皮恢复中具有重要和必要的作用。人乳中存在大量的TFF。这项研究旨在确定从人母乳中分离的TFF3与三叶处理的肠上皮细胞HT-29中的细胞因子(IL8和IL6)和防御素(hBD2和hBD4)水平之间可能存在相关性。产后2-4周内,通过人工乳房按摩从健康的人类母亲(18-30岁)中采集人乳样品,并通过硫酸铵沉淀,等电沉淀,DEAE色谱和凝胶过滤纯化TFF3。在这项工作中,我们分别通过免疫测定(ELISA)和半定量RT-PCR技术测量了细胞因子和防御素的浓度和mRNA水平。我们还测量了过氧化物酶活性。我们提供了人乳TFF3纯化的第一个证据。在这里,我们显示从牛奶中分离出的TFF3的存在与人肠上皮细胞中IL8和IL6的下调密切相关。另一方面,TFF3激活文化中的上皮细胞以产生β防御素2(hBD2)和β防御素4(hBD4)。这些发现表明,TFF可以通过诱导与先天防御相关的肽(如防御素)的产生来激活肠道上皮细胞,并可以积极参与母乳喂养的婴儿的免疫系统。

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