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Short\u2010 (0.5\u2003h) and long\u2010 (24\u2003h) term exposure of Caco\u20102 cells to IFN\u2010<jats:italic>\u03b3<\/jats:italic> resulted in a concentration\u2010dependent decrease in NHE activity. Inhibition of NHE activity by IFN\u2010<jats:italic>\u03b3<\/jats:italic> was absent in cariporide\u2010treated cells, but not in cells treated with S\u20103226. The long\u2010term exposure to IFN\u2010<jats:italic>\u03b3<\/jats:italic> was accompanied by a 20% increase in surface NHE1 abundance and no changes in total NHE1 abundance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of Raf1, mitogen\u2010activated protein kinase kinase (MAPKK\/MEK) and p38 MAPK with, respectively, GW 5074, PD 98059 and SB 203580 and downregulation of protein kinase C (PKC) with phorbol\u201012,13\u2010dibutyrate (100\u2003n<jats:sc>M<\/jats:sc> for 24\u2003h) prevented inhibition of NHE activity by IFN\u2010<jats:italic>\u03b3<\/jats:italic> (0.5 and 24\u2003h exposure). The signal transducer and activator transcription factor 1 (STAT1) inhibitor epigallocatechin\u20103\u2010gallate (EGCG) prevented inhibition of NHE activity by long\u2010 but not the short\u2010term treatment with IFN\u2010<jats:italic>\u03b3<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Treatment with IFN\u2010<jats:italic>\u03b3<\/jats:italic> activated phospho\u2010p38 MAPK, this effect being detected as early as 1\u2003h, persisting over 3\u2003h and decreasing after 24\u2003h. IFN\u2010<jats:italic>\u03b3<\/jats:italic> produced a sustained action of phospho\u2010STAT1 that was prevented by EGCG and partially attenuated by SB 203580 and insensitive to downregulation of PKC.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, short\u2010 and long\u2010term inhibition of NHE1 activity by IFN\u2010<jats:italic>\u03b3<\/jats:italic> involves a complex signaling pathway that includes PKC activation and STAT1 phosphorylation, respectively, but is not accompanied by downregulation of NHE1.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>145<\/jats:bold>, 93\u2013103. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706167\">10.1038\/sj.bjp.0706167<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706167","type":"journal-article","created":{"date-parts":[[2005,2,21]],"date-time":"2005-02-21T11:35:57Z","timestamp":1108985757000},"page":"93-103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Signaling of short\u2010 and long\u2010term regulation of intestinal epithelial type 1 Na<sup>+<\/sup>\/H<sup>+<\/sup> exchanger by interferon\u2010<i>\u03b3<\/i>"],"prefix":"10.1111","volume":"145","author":[{"given":"Fernando","family":"Magro","sequence":"first","affiliation":[]},{"given":"S\u00f3nia","family":"Fraga","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcio","family":"Soares\u2010da\u2010Silva","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.4049\/jimmunol.150.6.2356","article-title":"IFN\u2010gamma modulation of epithelial barrier function: time course, reversibility, and site of cytokine binding","volume":"150","author":"ADAMS R.B.","year":"1993","journal-title":"J. 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