title: Tryptase disturbs endocytic allergen degradation in intestinal epithelial cells.
abstract: It is noticed that mast cell activation can compromise epithelial barrier function, enabling antigens to be transported to the deep tissue of the intestine; the underlying mechanism is to be further elucidated. The current study aimed to investigate the mechanism by which the mast cell-derived mediator, tryptase, interferes with the degradation of the endocytic antigen in the intestinal epithelial cells. Intestinal epithelial cell lines were cultured into monolayers. The transepithelial resistance (TER) and permeability were assessed. The fusion of endosome and lysosome in epithelial cells was observed by immunocytochemistry. The antigenicity of protein antigens was tested by flow cytometry. The results showed that the expression of ubiquitin E3 ligase A20 (A20) was weakly expressed by naive gut epithelial cells and was markedly suppressed on exposure to tryptase in the culture. The presence of tryptase greatly disturbed the fusion of antigen-carrying endosomes and lysosomes in the epithelial cells, resulting in epithelial barrier dysfunction and a large quantity of antigen with functional antigenicity to be transported across the epithelial barrier. We conclude that tryptase can suppress the production of A20 in the intestinal epithelial cell lines, playing a critical role in intestinal epithelial monolayer barrier dysfunction.
authors.affiliation: Department of Digestive Endoscopy, Division of South Building, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
mesh_terms: D000485:Allergens / Q000378:metabolism*; D018938:Caco-2 Cells; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007422:Intestines / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D015398:Signal Transduction; D053802:Tryptases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D000485:Allergens; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D053802:Tryptases