title: IFN-gamma downregulates expression of Na(+)/H(+) exchangers NHE2 and NHE3 in rat intestine and human Caco-2/bbe cells.
abstract: Diarrhea associated with inflammatory bowel diseases has traditionally been attributed to stimulated secretion. The purpose of this study was to determine whether chronic stimulation of intestinal mucosa by interferon-gamma (IFN-gamma) affects expression and function of the apical membrane Na(+)/H(+) exchangers NHE2 and NHE3 in rat intestine and Caco-2/bbe (C2) cells. Confluent C2 cells expressing NHE2 and NHE3 were treated with IFN-gamma for 2, 24, and 48 h. Adult rats were injected with IFN-gamma intraperitoneally for 12 and 48 h. NHE2 and NHE3 activities were measured by unidirectional (22)Na influx across C2 cells and in rat brush-border membrane vesicles. NHE protein and mRNA were assessed by Western and Northern blotting. IFN-gamma treatment of C2 monolayers caused a >50% reduction in NHE2 and NHE3 activities and protein expression. In rats, region-specific, time- and dose-dependent reductions of NHE2 and NHE3 activities, protein expression, and mRNA were observed after exposure to IFN-gamma. Chronic exposure of intestinal epithelial cells to IFN-gamma results in selective downregulation of NHE2 and NHE3 expression and activity, a potential cause of inflammation-associated diarrhea.
authors: The Martin Boyer Laboratories, University of Chicago, Chicago, Illinois 60637, USA.
authors: F
authors: F
authors: Rocha
authors: M W
authors: MW
authors: Musch
authors: L
authors: L
authors: Lishanskiy
authors: C
authors: C
authors: Bookstein
authors: K
authors: K
authors: Sugi
authors: Y
authors: Y
authors: Xie
authors: E B
authors: EB
authors: Chang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007082:Ileum; D007371:Interferon-gamma / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008871:Microvilli / Q000502:physiology; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C081517:SLC9A2 protein, human; C000613385:SLC9A3 protein, human; C513110:Slc9a2 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D007371:Interferon-gamma; D012964:Sodium