Cholera Toxin Suppresses Expression of Ubiquitin Editing Enzyme A20 and Enhances Transcytosis

Abstract

Background: The ubiquitin editing enzyme A20 plays an important role in maintaining the homeostasis in the body Microbe-derived adjuvants are commonly used in animal models of intestinal allergy. Objective: This study aims to investigate the role of cholera toxin-induced A20 suppression in compromising intestinal barrier function. Methods: Human intestinal epithelial cells were cultured into monolayers as an in vitro epithelial barrier model. Ovalbumin (OVA) was used as a specific allergen to test the degrading capability of intestinal epithelial cells for the endocytic allergens. The fusion of endosomes and lysosomes in epithelial cells was observed by immunocytochemistry. The antigenicity of OVA was tested by T cell proliferation assay. Results: A20 was detectable in the intestinal cell lines and mouse intestinal epithelialum. A20 was required in the degradation of endocytic allergens in HT-29 cells. The allergen, OVA, could pass through A20-deficient HT-29 monolayer barrier. Exposure to microbial adjuvant, cholera toxin, suppressed the expression of A20 in HT-29 cells, which compromised the epithelial barrier function. Conclusion: The microbial product, cholera toxin, interferes with the expression of A20 in intestinal epithelial cells, which compromises the intestinal epithelial barrier function.

Alphavbeta6 is required in maintaining the intestinal epithelial barrier function

“…Cumulative evidence shows incompetent of epithelial cells in the degradation of the endocytic proteins under given circumstances (Huang et al, ; Li et al, ; Liao et al, ) that results in epithelial barrier dysfunction. We considered whether additional avb6 facilitates the degradation of the endocytic antigens under circumstances such as in high levels of proinflammatory cytokines.…”

“…The epithelial barrier dysfunction occurs when macromolecular molecules, such as protein antigens, fail to pass through the epithelial barrier to arrive at the deep tissues of the body, such as the subepithelial region, where the antigens may contact various immune cells and initiate aberrant immune responses and immune inflammation. A number of factors are recognized associating with epithelial barrier dysfunction, including psychological stress (Zheng et al, ; Yu et al, ), exposure to microbial products (Li et al, ; Liu et al, ), allergy (Rezaee et al, ; Liu et al, ; Post et al, ) and chronic inflammation (Gersemann et al, ). To date, the underlying mechanism of epithelial barrier dysfunction is not fully understood.…”

Staphylococcal enterotoxin B suppresses Alix and compromises intestinal epithelial barrier functions

“…Epithelial cells express CD23 on the surface that facilitates the transcellular transport of specific antigens across the epithelial barrier [12,13]. Recent reports indicate that exposure to microbial products also affects the epithelial barrier functions [5,8]. The present study adds novel information to this area by showing that Alix is required in the maintenance of the epithelial barrier function.…”

“…Under healthy condition, epithelial cells endocytose some proteins of small molecular weight; those endocytic cargo can be wrapped by the plasma membranes to be formed as endosomes; the latter fuse with lysososmes where there are acidic enzymes to degrade the endocytic cargo. Recent reports indicate that there are a number of factors can affect the endolysosome systems to enhance the epithelial barrier permeability [5-7]; the causative factors include microbial products, such as cholera toxin [5] and SEB [8]. The underlying mechanism remains to be further understood.…”

Interleukin-13 suppresses interleukin-10 via inhibiting A20 in peripheral B cells of patients with food allergy

“…The deficiency of A20 promoted intestinal allergy [14]. Li et al observed that exposure to cholera toxin suppressed the expression of A20, which resulted in compromising epithelial barrier function [27]. Vereecke et al found that deficiency of A20 promoted the development of colitis in mice [28].…”