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The gliadin p31–43 peptide: Inducer of multiple proinflammatory effects
International Review of Cell and Molecular Biology Pub Date : 2020-11-05 , DOI: 10.1016/bs.ircmb.2020.10.003
Fernando Gabriel Chirdo 1 , Salvatore Auricchio 2 , Riccardo Troncone 3 , Maria Vittoria Barone 3
Affiliation  

Coeliac disease (CD) is the prototype of an inflammatory chronic disease induced by food. In this context, gliadin p31–43 peptide comes into the spotlight as an important player of the inflammatory/innate immune response to gliadin in CD. The p31–43 peptide is part of the p31–55 peptide from α-gliadins that remains undigested for a long time, and can be present in the small intestine after ingestion of a gluten-containing diet. Different biophysical methods and molecular dynamic simulations have shown that p31–43 spontaneously forms oligomeric nanostructures, whereas experimental approaches using in vitro assays, mouse models, and human duodenal tissues have shown that p31–43 is able to induce different forms of cellular stress by driving multiple inflammatory pathways. Increased proliferative activity of the epithelial cells in the crypts, enterocyte stress, activation of TG2, induction of Ca2 +, IL-15, and NFκB signaling, inhibition of CFTR, alteration of vesicular trafficking, and activation of the inflammasome platform are some of the biological effects of p31–43, which, in the presence of appropriate genetic susceptibility and environmental factors, may act together to drive CD.



中文翻译:

麦醇溶蛋白 p31-43 肽:多种促炎作用的诱导剂

乳糜泻 (CD) 是由食物引起的炎症性慢性疾病的原型。在这种情况下,麦醇溶蛋白 p31-43 肽作为对 CD 中麦醇溶蛋白的炎症/先天免疫反应的重要参与者而受到关注。p31-43 肽是来自 α-醇溶蛋白的 p31-55 肽的一部分,它长时间不被消化,并且可以在摄入含麸质饮食后存在于小肠中。不同的生物物理方法和分子动力学模拟表明 p31-43 自发形成寡聚纳米结构,而使用体外实验方法分析、小鼠模型和人类十二指肠组织表明,p31-43 能够通过驱动多种炎症途径诱导不同形式的细胞应激。隐窝中上皮细胞的增殖活性增加、肠细胞应激、TG2 的激活、Ca 2  +、IL-15 和 NFκB 信号传导的诱导、CFTR 的抑制、囊泡运输的改变和炎性体平台的激活是其中的一些p31-43 的生物学效应,在存在适当的遗传易感性和环境因素的情况下,可能共同作用以驱动 CD。

更新日期:2020-11-05
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