{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T01:14:47Z","timestamp":1776215687151,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,1,28]],"date-time":"2003-01-28T00:00:00Z","timestamp":1043712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:p><jats:bold>Abstract:<\/jats:bold><jats:italic>Background\/Aims:<\/jats:italic>In primary biliary cirrhosis (PBC), cytokines from<jats:styled-content>CD4<\/jats:styled-content><jats:sup>\u2003+\u2003<\/jats:sup><jats:styled-content>T<\/jats:styled-content>lymphocytes were suggested to contribute to the intralobular bile duct damage together with cellular immunity by<jats:styled-content>CD8<\/jats:styled-content><jats:sup>\u2003+\u2003<\/jats:sup><jats:styled-content>T<\/jats:styled-content>lymphocytes. Recently, we reported that immunolocalization of 7H6 \u2013 a tight junction (TJ)\u2010associated protein \u2013 was significantly diminished in cholangiocytes in the PBC liver. In this study, we examined the direct effects of several cytokines \u2013 tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interferon\u2010\u03b3 (IFN\u2010\u03b3), interleukin\u20102 and 4 (IL\u20102 and 4) \u2013 on TJ in immortalized mouse cholangiocytes. Moreover, we examined the inhibitory effect of ursodeoxycholic acid<jats:styled-content>(UDCA)<\/jats:styled-content>on cytokine\u2010induced changes in paracellular permeability.<jats:italic>Methods:<\/jats:italic>Barrier function of TJ was evaluated by measuring transepithelial electrical resistance (TER) and<jats:sup>3<\/jats:sup>H\u2010inulin flux. We also performed immunostaining and immunoblotting for TJ\u2010associated proteins \u2013 claudin\u20101 and \u20103, occludin, zonula occluden\u20101 (ZO\u20101) and 7H6.<jats:italic>Results:<\/jats:italic>TNF\u2010\u03b1 and IFN\u2010\u03b3, but neither IL\u20102 nor IL\u20104, significantly decreased TER (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.005).<jats:sup>3<\/jats:sup>H\u2010inulin flux studies confirmed IFN\u2010\u03b1\u2010induced increases in paracellular permeability of cholangiocytes (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). In immunostaining and immunoblotting studies, TJ\u2010associated proteins were well preserved in TNF\u2010\u03b1\u2010 or IFN\u2010\u03b3\u2010treated cells. Ursodeoxycholic acidhas been found to have no inhibitory effect on increased paracellular permeability induced by TNF\u2010\u03b1 or IFN\u2010\u03b3.<jats:italic>Conclusion:<\/jats:italic>These findings show that TNF\u2010\u03b1 and IFN\u2010\u03b3 disrupt barrier function of TJ in cholangiocytes without major structural changes to TJ and suggest that disruption of TJ function and subsequent leakage of the bile constituents may influence the aggravation of cholestasis in PBC.<\/jats:p>","DOI":"10.1034\/j.1600-0676.2003.01707.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T10:24:47Z","timestamp":1047464687000},"page":"3-11","source":"Crossref","is-referenced-by-count":53,"title":["Tumor necrosis factor\u2010\u03b1 and interferon\u2010\u03b3 directly impair epithelial barrier function in cultured mouse 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