A Prospective Comparison Between 1.5t Magnetic Resonance and 3t Magnetic Resonance in Ileo-Colonic Crohn's Disease: A Single Center Experience

Abstract

Studies using animal models suggest that proteolytic balance at the surface of inflamed mucosa is broken towards an increased proteolytic activity. This increase could be explained by an important release of active proteases, a decreased expression of endogenous protease inhibitors, or both. We have investigated here the proteolytic activity released by fresh colonic tissue biopsies of IBD patients (Crohn's disease: CD, and Ulcerative Colitis: UC) and non-IBD patients, and we have investigated in those tissues, the expression of Elafin, an endogenous serine protease inhibitor, possibly released by many cell types. This molecule is considered as an “alarm” antiprotease released by immune or epithelial cells, and that is able to inhibit neutrophil proteases such as elastase and Proteinase-3. Methods: Non-IBD patients (Control), CD and UC colonic biopsies were harvested and freshly incubated for 1-h at 37 degrees, in culture media (HBSS). Arginin cleavage specific activity was measured in biopsy supernatants using a chromogenic substrate (tosyl-GPR-pNa). Other biopsies were paraffin-embedded and used for the detection of elafin mRNA using sense and antisense RNA riboprobes (200pb) against elafin mRNA. Results: A significant increased proteolytic activity was detected in culture supernatants from CD, and UC biopsies compared to control patients supernatants. In non-inflamed biopsies, we detected a strong expression of elafin mRNA in epithelium while only few cells in the sub-mucosa expressed this mRNA. In both UC and CD biopsies, elafin mRNA was detected in the sub-mucosa in a zone that correlated with infiltrated immune cells. However in the intestinal epithelium itself, elafin mRNA expression was clearly reduced. Conclusion:Our results showed that in IBD patients, proteolytic balance of the mucosa is disrupted towards an increased proteolytic activity. Elafin mRNA was constitutively expressed by epithelial cells in non-IBD patient tissues, but in IBD patient tissues, a specific down-regulation of elafin expression was observed in the epithelium. This study showed that the intestinal protease-antiprotease balance is altered in inflammatory bowel disease (IBD) and proposes that deficient expression of elafin by the epithelium could participate to explain this unbalance.