Dynamics of enterocyte tight junctions: effect of experimental colitis and two different anti-TNF strategies.

An alteration of the intestinal barrier is considered to represent an early step in pathogenesis of Crohn’s disease. The integrity of intestinal barrier function is guaranteed among other factors by enterocyte tight junction (TJ) proteins. Clin- ical and experimental data indicate the TNF- to be the major responsible factor for these defects. In the present study we investi- gated the very early effects of DNBS-ethanol colitis on ileal entero- cyte TJ proteins [occludin, zonula occludens-1 (ZO-1), claudin-2] in controls, mice treated with infliximab (IFX) or with etanercept (ETC), and in knockout mice for the TNF- receptor 1 (TNFR-1 / ). Circulating TNF- levels were effectively reduced by IFX and ETC (P 0.01, both) at 3 and at 6 h. DNBS colitis induced disappearance of occludin and ZO-1 from enterocyte cell-cell contact, whereas claudin-2, absent under control conditions, appeared in the ileal epithelium. These alterations were prevented equally by both treat- ments, IFX and ETC, and in TNFR-1/ animals. DNBS colitis induced a very rapid loss of occludin and ZO-1 from ileal TJ together with an upregulation of claudin-2. Our data are consistent with the hypothesis that TNF- is involved in early TJ rearrangement and that its effects are mediated through TNFR-1. Despite clinical differences, both anti-TNF treatments were equally effective in the present setting.