{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:54:53Z","timestamp":1791352493019,"version":"4.3.1"},"reference-count":37,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n                    <jats:bold>Background and aims:<\/jats:bold>\n                    Barrier dysfunction is an important feature contributing to inflammation and diarrhoea in Crohn\u2019s disease (CD). Recently, tumour necrosis factor \u03b1 (TNF-\u03b1) antibodies were recognised as effective in steroid refractory CD. The aim of this study was to characterise the effects of this therapy on the epithelial barrier.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Patients and methods:<\/jats:bold>\n                    Forceps biopsies were obtained from the sigmoid colon before and 14 days after TNF-\u03b1 antibody therapy in 11 patients treated for chronic active CD (Crohn\u2019s disease activity index &gt;150). Epithelial apoptoses were measured after terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) and 4\u2032,6-diamidino-2-phenylindole staining. Epithelial resistance was determined by alternating current impedance analysis in miniaturised Ussing chambers. Occludin, claudin 1, and claudin 4 expression was quantified in immunoblots.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The epithelial apoptotic ratio was 2.1 (0.2)% in controls and increased to 5.3 (1.0)% in CD. TNF-\u03b1 antibody therapy decreased the apoptotic ratio to 2.9 (1.0)% (normalised in 10 of 11 patients). In parallel, epithelial resistance was lower in CD than in controls (24 (3)\n                    <jats:italic>v<\/jats:italic>\n                    42 (3) \u03a9\u00d7cm\n                    <jats:sup>2<\/jats:sup>\n                    ) and improved to 34 (3) \u03a9\u00d7cm\n                    <jats:sup>2<\/jats:sup>\n                    after therapy. Occludin, claudin 1, and claudin 4 were not affected by TNF-\u03b1 antibody therapy. In support of a functional role of epithelial apoptoses in CD, a similar decrease in resistance of \u221240% was observed when the apoptotic rate was selectively upregulated from 2.6% to 5.4% with camptothecin in HT-29\/B6 cells.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Epithelial apoptoses were upregulated in the colon in CD and restored to normal in 10 of 11 patients by TNF-\u03b1 antibody therapy. This is the structural correlate of epithelial barrier dysfunction measured as epithelial resistance while expression of tight junction proteins did not contribute to this therapeutic effect.\n                  <\/jats:p>","DOI":"10.1136\/gut.2003.036632","type":"journal-article","created":{"date-parts":[[2004,8,11]],"date-time":"2004-08-11T19:02:47Z","timestamp":1092250967000},"page":"1295-1302","source":"Crossref","is-referenced-by-count":261,"title":["Downregulation of epithelial apoptosis and barrier repair in active Crohn\u2019s disease by tumour necrosis factor \u03b1 antibody 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