title: NHE8 plays an important role in mucosal protection via its effect on bacterial adhesion.
abstract: The Na⁺/H⁺ exchanger NHE8 is expressed on the apical membrane of intestinal epithelial cells and is particularly abundant in the colon. Our previous study showed that Muc2 expression was significantly reduced in NHE8-knockout (NHE8-/-) mice, suggesting that NHE8 plays a role in mucosal protection in the colon. The current study confirms and extends our studies on the role of NHE8 in mucosal protection. The number of bacteria attached on the distal colon was significantly increased in NHE8-/- mice compared with their wild-type littermates. As expected, IL-4 expression was markedly increased in NHE8-/- mice compared with wild-type mice. Immunohistochemistry showed disorganization in the mucin layer of NHE8-/- mice, suggesting a possible direct bacteria-epithelia interaction. Furthermore, NHE8-/- mice were susceptible to dextran sodium sulfate-induced mucosal injury. In wild-type mice, dextran sodium sulfate treatment inhibited colonic NHE8 expression. In Caco-2 cells, the absence of NHE8 expression resulted in higher adhesion rates of Salmonella typhimurium but not Lactobacillus plantarum. Similarly, in vivo, S. typhimurium adhesion rate was increased in NHE8-/- mice compared with wild-type mice. Our study suggests that NHE8 plays important roles in protecting intestinal epithelia from infectious bacterial adherence.
authors: Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724, USA.
authors: Chang
authors: C
authors: Liu
authors: Hua
authors: H
authors: Xu
authors: Bo
authors: B
authors: Zhang
authors: Malin E V
authors: ME
authors: Johansson
authors: Jing
authors: J
authors: Li
authors: Gunnar C
authors: GC
authors: Hansson
authors: Fayez K
authors: FK
authors: Ghishan
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification; D001422:Bacterial Adhesion / Q000502:physiology*; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C471945:Slc9a8 protein, mouse; D017923:Sodium-Hydrogen Exchangers; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate
keywords: NHE8; Salmonella; mucosal layer
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