Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrier function

Abstract

The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 (Trek1) in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic (Clostridium butyricum) restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.

Neutralization of IL-6 and TNF-α ameliorates intestinal permeability in DSS-induced colitis

“…One mechanism is depended on transcriptional and enzymatic activation of epithelial MLCK that leads to phosphorylation of MLC [13][14][15]. The other mechanism of barrier loss is associated with increased epithelial claudin-2 expression [16][17][18]. We here evaluated MLCK and claudin-2 expression in mice colons.…”

Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor–Dependent Repression of Claudin-2

“…While we do not know the exact nature of this additional signaling, it is possible that HDACi activity of butyrate could be involved. Butyrate was recently shown to promote barrier in T84 cells via HDAC inhibition and induction of TWIK-related potassium channel-1 (Trek1) (51). …”

Transfer of CD11c+ lamina propria mononuclear phagocytes from post-infectious irritable bowel syndrome causes mucosal barrier dysfunction and visceral hypersensitivity in recipient mice

“…As the primary barrier, the intestine is exposed to a wide variety of antigens and bacteria, and it plays an important role in maintaining homeostasis in the body. Abnormal CD11c + mononuclear phagocytes, such as dendritic cells (DCs), macrophages, and monocytes, are involved in the disruption of immune tolerance in organisms, which can lead to the development of chronic inflammatory diseases, including Crohn's disease and others (21,22). Notably, different subtypes of mononuclear phagocytic cells play different roles.…”