title: Interferon-gamma induces a cell surface phenotype switch on T84 intestinal epithelial cells.
abstract: Intestinal epithelia are in intimate contact with submucosal and intraepithelial lymphocytes. The concentration of intraepithelial lymphocytes increases during inflammatory processes, and, when stimulated, these cells generate cytokines such as interferon-gamma (IFN-gamma). In this study, we examined the effect of recombinant human IFN-gamma on ion transport events in T84 cells, a crypt epithelial cell line widely used to study electrogenic Cl- secretion, the transport event responsible for mucosal hydration. Epithelial exposure to IFN-gamma brought about a marked attenuation in stimulated Cl- secretion, as measured by generation of short-circuit current (ISC). This IFN-gamma-elicited decrease in the Cl- secretory response was present for a variety of specific agonists, appeared largely due to IFN-gamma interactions with the basolateral surface, and did not result from a defect in second messenger generation. Efflux and uptake studies were utilized to functionally define the individual cell surface transport proteins that participate in Cl- secretion and revealed that, in response to epithelial exposure to IFN-gamma, apical Cl- channels and basolateral Na(+)-K(+)-2Cl- cotransporters, K+ channels, and Na-K-adenosinetriphosphatase were all functionally downregulated. [3H]bumetanide binding assays suggested that surface expression of the cotransporter was diminished by > 70% after IFN-gamma preexposure. Concurrently, surface immunofluorescence studies revealed that epithelial exposure to IFN-gamma brought about the induction of major histocompatibility complex (MHC) class II molecule expression on T84 epithelial monolayers and markedly increased MHC class I surface expression. Finally, neutrophil-epithelial adhesion studies revealed that preexposure of epithelial monolayers to IFN-gamma elicited a beta 2-integrin-dependent induction of neutrophil adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: S P
authors.initials: SP
authors.lastname: Colgan
authors.forename: C A
authors.initials: CA
authors.lastname: Parkos
authors.forename: J B
authors.initials: JB
authors.lastname: Matthews
authors.forename: L
authors.initials: L
authors.lastname: D'Andrea
authors.forename: C S
authors.initials: CS
authors.lastname: Awtrey
authors.forename: A H
authors.initials: AH
authors.lastname: Lichtman
authors.forename: C
authors.initials: C
authors.lastname: Delp-Archer
authors.forename: J L
authors.initials: JL
authors.lastname: Madara
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D006680:HLA Antigens; D007371:Interferon-gamma