title: 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.
authors: Department of Gastroenterology, the Second Hospital, Zhengzhou University, Zhengzhou, China.
authors: Huang
authors: H
authors: Huang
authors: ENT Institute, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen, China.|ENT Hospital, Longgang Central Hospital, Shenzhen, China.|Brain Body Institute, McMaster University, Hamilton, ON, Canada.
authors: Jiang-Qi
authors: JQ
authors: Liu
authors: Department of Gastroenterology, the Second Hospital, Zhengzhou University, Zhengzhou, China.
authors: Yong
authors: Y
authors: Yu
authors: ENT Institute, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen, China.
authors: Li-Hua
authors: LH
authors: Mo
authors: Brain Body Institute, McMaster University, Hamilton, ON, Canada.
authors: Rong-Ti
authors: RT
authors: Ge
authors: Brain Body Institute, McMaster University, Hamilton, ON, Canada.
authors: Huan-Ping
authors: HP
authors: Zhang
authors: ENT Institute, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen, China.
authors: Zhi-Gang
authors: ZG
authors: Liu
authors: Department of Gastroenterology, the Second Hospital, Zhengzhou University, Zhengzhou, China.
authors: Peng-Yuan
authors: PY
authors: Zheng
authors: ENT Institute, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen, China.|Brain Body Institute, McMaster University, Hamilton, ON, Canada.
authors: Ping-Chang
authors: PC
authors: Yang
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D002460:Cell Line; D046972:Clostridium butyricum / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin; D024683:Potassium Channels, Tandem Pore Domain / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D019936:Probiotics / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D020148:Butyric Acid; C012589:trichostatin A; D010047:Ovalbumin; D020928:Mitogen-Activated Protein Kinases; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1