{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:17:05Z","timestamp":1762100225604},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1642,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>This study evaluated the effects of human interferon\u2010<jats:italic>\u03b3<\/jats:italic> (IFN\u2010<jats:italic>\u03b3<\/jats:italic>) on Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity and the intracellular signaling pathways involved in human intestinal epithelial Caco\u20102 cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity was determined as the difference between total and ouabain\u2010sensitive ATPase. p38 MAP kinase activity was analyzed by Western blotting using the p38 MAP kinase assay kit. Total and phosphorylated STAT1 protein levels were detected using the PhosphoPlus\u00ae Stat1.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>IFN\u2010<jats:italic>\u03b3<\/jats:italic> decreased Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity in a time\u2010 and concentration\u2010dependent manner. The IFN\u2010<jats:italic>\u03b3<\/jats:italic>\u2010induced decrease in Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity was accompanied by no changes in the abundance of <jats:italic>\u03b1<\/jats:italic><jats:sub>1<\/jats:sub> subunit Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase. Downregulation of protein kinase C (PKC) with phorbol\u201012,13\u2010dibutyrate (PDBu) prevented the inhibitory effect of IFN\u2010<jats:italic>\u03b3<\/jats:italic> on Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity. Inhibition of Raf\u20101, mitogen\u2010activated protein kinase kinase (MAPKK\/MEK), p38 MAPK and STAT1 with, respectively, GW 5074, PD 98059, SB 203580 and epigallocatechin gallate prevented inhibition of Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity by 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> markedly increased the expression of total and phospho\u2010STAT1, this being accompanied by activation of p38 MAPK. Activation of phospho\u2010STAT1 by IFN\u2010<jats:italic>\u03b3<\/jats:italic> was almost abolished by epigallocatechin gallate and markedly reduced by SB 203580, but insensitive to downregulation of PKC.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The increase in short circuit current (<jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub>) by 1.0 and 2.5 <jats:italic>\u03bc<\/jats:italic>g ml<jats:sup>\u22121<\/jats:sup> amphotericin B was markedly attenuated in IFN\u2010<jats:italic>\u03b3<\/jats:italic>\u2010treated cells. However, the inhibitory effect of PDBu on the amphotericin B\u2010induced increase in <jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub> was of similar magnitude in vehicle\u2010 and IFN\u2010<jats:italic>\u03b3<\/jats:italic>\u2010treated cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that IFN\u2010<jats:italic>\u03b3<\/jats:italic> markedly attenuates Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2013ATPase activity. The transduction mechanisms set into motion by IFN\u2010<jats:italic>\u03b3<\/jats:italic> involve the activation of PKC downstream STAT1 phosphorylation and Raf\u20101, MEK, ERK2 and p38 MAPK pathways, in a complex sequence of events.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>142<\/jats:bold>, 1281\u20131292. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705895\">10.1038\/sj.bjp.0705895<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705895","type":"journal-article","created":{"date-parts":[[2004,8,12]],"date-time":"2004-08-12T12:10:14Z","timestamp":1092312614000},"page":"1281-1292","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intestinal Na<sup>+<\/sup>\u2013K<sup>+<\/sup>\u2013ATPase activity and molecular events downstream of interferon\u2010<i>\u03b3<\/i> receptor stimulation"],"prefix":"10.1111","volume":"142","author":[{"given":"Fernando","family":"Magro","sequence":"first","affiliation":[]},{"given":"S\u00f3nia","family":"Fraga","sequence":"additional","affiliation":[]},{"given":"Tom\u00e9","family":"Ribeiro","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. Immunol."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01031-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"18119","DOI":"10.1016\/S0021-9258(18)55244-3","article-title":"Interferon\u2010gamma\u2010induced astrocyte class II major histocompatibility complex gene expression is associated with both protein kinase C activation and Na+ entry","volume":"266","author":"BENVENISTE E.N.","year":"1991","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.5.C1398"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00445.x"},{"key":"e_1_2_7_7_1","first-page":"127","article-title":"Interleukin\u20102\u2010 and interferon\u2010gamma\u2010secreting T cells in normal and diseased human intestinal mucosa","volume":"78","author":"BREESE E.","year":"1993","journal-title":"Immunol. Today"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(200005)30:5<1486::AID-IMMU1486>3.0.CO;2-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109924200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"C402","DOI":"10.1152\/ajpcell.1994.267.2.C402","article-title":"Interferon\u2010gamma induces a cell surface phenotype switch on T84 intestinal epithelial cells","volume":"267","author":"COLGAN S.P.","year":"1994","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.16500"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.8.1169"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.5.C1313"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.45.2.191"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103484200"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.8.1901"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70392-6"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.278.5.G700"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.20.5601"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00244.2001"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00318.2001"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.1.R10"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(99)01510-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117895"},{"key":"e_1_2_7_25_1","first-page":"14","article-title":"Signal transduction in the interferon system","volume":"25","author":"HAQUE S.J.","year":"1998","journal-title":"Semin. Oncol."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005926200"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510289"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(99)00668-X"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"C127","DOI":"10.1152\/ajpcell.1995.268.1.C127","article-title":"Role of protein kinase C and tyrosine kinase activity in IFN\u2010gamma\u2010induced expression of the class II MHC gene","volume":"268","author":"LEE Y.J.","year":"1995","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"C1256","DOI":"10.1152\/ajpcell.1996.271.4.C1256","article-title":"Potentiation by thyroxine of interferon\u2010gamma\u2010induced antiviral state requires PKA and PKC activities","volume":"271","author":"LIN H.Y.","year":"1996","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1128\/iai.62.7.2722-2731.1994","article-title":"Gamma interferon induces rapid and coordinate activation of mitogen\u2010activated protein kinase (extracellular signal\u2010regulated kinase) and calcium\u2010independent protein kinase C in human monocytes","volume":"62","author":"LIU M.K.","year":"1994","journal-title":"Infect. Immun."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113938"},{"key":"e_1_2_7_33_1","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1096\/fj.00-0519fje","article-title":"Anti\u2010interferon gamma action of epigallocatechin\u20103\u2010gallate mediated by specific inhibition of STAT1 activation","volume":"15","author":"MENEGAZZI M.","year":"2002","journal-title":"FASEB J."},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.5.1281"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1042\/bj3490427","article-title":"Interferons activate the p42\/44 mitogen\u2010activated protein kinase and JAK\u2010STAT (Janus kinase\u2010signal transducer and activator transcription factor) signalling pathways in hepatocytes: differential regulation by acute ethanol via a protein kinase C\u2010dependent mechanism","volume":"349","author":"NGUYEN V.A.","year":"2000","journal-title":"Biochem. J."},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1995.tb03130.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.22.2.153"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192264999"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.280.5.C1224"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.12.6586"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)91235-X"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.7.3833"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.30.18701"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.24045"},{"key":"e_1_2_7_45_1","first-page":"G913","article-title":"Mechanism of inhibition of Na+\u2010glucose cotransport in the chronically inflamed rabbit illeum","volume":"273","author":"SUNDARAM U.","year":"1997","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2003.03024.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201477"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199507000-00004"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.12.5984"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(01)01282-6"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.6.F1033"},{"key":"e_1_2_7_52_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1042\/bj3050425","article-title":"Role of protein kinase C activation in synthesis of complement components C2 and factor B in interferon\u2010gamma\u2010stimulated human fibroblasts, glioblastoma cell line A172 and monocytes","volume":"305","author":"WATANABE I.","year":"1995","journal-title":"Biochem. J."},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.6.G1323"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.13.7460"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705895","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705895","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0705895","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T21:36:40Z","timestamp":1697233000000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0705895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":53,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1038\/sj.bjp.0705895"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0705895","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}