• Crohn's disease;
  • experimental colitis;
  • epithelial barrier function;
  • cytokines;
  • indomethacin



Epithelial barrier disturbance is thought to contribute to the pathogenesis of inflammatory bowel diseases; however, it remains unclear whether it is a primary defect participating to the onset of inflammation or only a consequence of sustained inflammation.


A time course study of epithelial barrier functions and immune mediators was performed in the CD4+CD45RBhi T cell transfer model of colitis using Ussing chambers.


In nonreconstituted severe combined immunodeficiency (SCID) mice, no epithelial dysfunction was observed. However, after transfer of CD4+CD45RBhi T cells or total CD4+ T cells, colon of SCID mice displayed a decreased epithelial resistance, even before overt microscopic inflammation had occurred. Sustained colitis of CD4+CD45RBhi T cell reconstituted mice was also associated with enhanced subepithelial resistance, enhanced paracellular permeability, and decreased net ion transport. All these reflect a disturbance of barrier function and may contribute to diarrhea. Epithelial resistance was positively correlated with interleukin 10 (IL-10) and transforming growth factor β (TGF-β) levels and net ion transport inversely correlated with tumor necrosis factor alpha (TNF-α) levels, pointing to the protective effect of IL-10 and TGF-β and to a damaging effect of TNF-α. Indomethacin, a nonselective COX inhibitor, decreased epithelial resistance independent of T cells and inflammation, but its effect was more pronounced in inflamed colon.


Induction of colitis by transfer of CD4+CD45RBhi T cells in SCID mice leads to changes in the colonic epithelium before colitis develops. Decreased epithelium resistance might contribute to the development of colitis; however, it is not sufficient to lead to chronic inflammation. (Inflamm Bowel Dis 2010)