泛素E3连接酶A20有助于维持上皮屏障功能。
Ubiquitin E3 ligase A20 contributes to maintaining epithelial barrier function.
作者信息
Huang Peixin, Geng Xiao-Rui, Yang Gui, Chen Chi, Liu Zhanju, Yang Ping-Chang
机构信息
Department of Gastroenterology, the Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
出版信息
Cell Physiol Biochem. 2012;30(3):702-10. doi: 10.1159/000341450. Epub 2012 Aug 1.
BACKGROUND AND AIMS
Epithelial barrier dysfunction is involved in the pathogenesis of allergic diseases; the mechanism is to be further understood. Ubiquitin E3 ligase A20 (A20) plays a role in maintaining the homeostasis in the body. This study aims to investigate the role of A20 in maintaining the epithelial barrier function.
METHODS
Human intestinal epithelial cell line, Caco-2 cells, was cultured to monolayers to test the endocytosis and degradation of a model allergen, ovalbumin (OVA). The role of A20 in the endosome/lysosome fusion in epithelial cells was tested with A20-sufficient and A20-deficient Caco-2 cells and visualized by immunocytochemistry.
RESULTS
Caco-2 cells could endocytose exogenous allergens (OVA) in culture. The endocytic OVA was degraded in A20-sufficient Caco-2 cells via the mechanism of endosome/lysosome fusion, while the A20-deficient Caco-2 monolayers converted the OVA to the basal compartment of transwells, which conserved the antigenicity reflected by that it induced T cell proliferation in an allergen-specific manner. A20 was required in the fusion of endosomes and lysosomes.
CONCLUSION
A20 contributes to maintaining the epithelial barrier function.
背景与目的
上皮屏障功能障碍参与过敏性疾病的发病机制；其机制有待进一步阐明。泛素E3连接酶A20（A20）在维持机体稳态中发挥作用。本研究旨在探讨A20在维持上皮屏障功能中的作用。
方法
将人肠上皮细胞系Caco-2细胞培养成单层，以检测模型变应原卵清蛋白（OVA）的内吞作用和降解情况。用A20充足和A20缺陷的Caco-2细胞检测A20在上皮细胞内体/溶酶体融合中的作用，并通过免疫细胞化学进行可视化观察。
结果
Caco-2细胞在培养中能够内吞外源性变应原（OVA）。内吞的OVA在A20充足的Caco-2细胞中通过内体/溶酶体融合机制被降解，而A20缺陷的Caco-2单层细胞将OVA转运至Transwell小室的基底隔室，这保留了其抗原性，表现为以变应原特异性方式诱导T细胞增殖。内体与溶酶体的融合需要A20。
结论
A20有助于维持上皮屏障功能。
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