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• W2017377943 abstract "Background & Aims: To determine how interferon (IFN)-γ inhibits epithelial barrier and ion transport functions, intestinal T84 cells were studied. Methods: Acute and chronic effects of IFN-γ on T84 barrier function, Na+,K+–adenosine triphosphatase (ATPase) activity, and certain ion transport and tight junctional proteins were determined. To assess the role of Na+,K+-ATPase and intracellular Na+, similar studies with the Na+,K+-ATPase inhibitor ouabain and Na+ ionophore monensin were performed. To determine the role of nitric oxide (NO), the NO donor SPER-NO was used. Results: IFN-γ acutely (<6 hour) decreased cellular Na+,K+-ATPase activity, followed later (>24 hours) by decreases in expression of Na/K/2Cl, the α subunit of Na+,K+-ATPase, occludin, and ZO-1. In contrast, cystic fibrosis transmembrane conductance regulator or the Na+ pump β subunit were unchanged. Ouabain and monensin caused nearly identical changes to IFN-γ. Incubation in low Na+ media significantly blunted the chronic effects of IFN-γ. Hypotonic-induced cell swelling, in contrast, had effects similar to IFN-γ but did not alter the expression of the Na+ pump α subunit. The NO donor SPER-NO rapidly inhibited Na+,K+-ATPase and also down-regulated transport and barrier proteins. Conclusions: IFN-γ inhibition of Na+,K+-ATPase activity acutely causes increases in intracellular Nai concentration and cell volume, which are distinct signaling events that ultimately result in a leaky and dysfunctional epithelium associated with chronic inflammation.GASTROENTEROLOGY 2001;120:1393-1403" @default.
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• W2017377943 date "2001-05-01" @default.
• W2017377943 modified "2023-10-14" @default.
• W2017377943 title "Inhibition of Na+,K+-ATPase by interferon γ down-regulates intestinal epithelial transport and barrier function" @default.
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• W2017377943 doi "https://doi.org/10.1053/gast.2001.24045" @default.
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