Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

摘要: Serine proteases elicit cellular responses via protease-activated receptor-2 (PAR-2) which is known to regulate inflammation and the immune response. Although gastrointestinal tract exposed large amounts of proteolytic enzymes, role PAR-2 in canine inflammatory bowel disease (IBD) remains unclear. The objective this study was investigate effects activation on cytokine/chemokine gene expression intestine intestinal fecal serine protease activity dogs with IBD. Duodenal biopsies from healthy were cultured treated ex vivo trypsin or agonist peptide, tissues then quantified by real-time PCR. mRNA protein levels duodenal mucosa examined PCR immunohistochemistry, respectively. Fecal determined azocasein assay. In vivo-cultured duodenum, peptide induced significant up-regulation interleukin-1 β (IL-1β), IL-8, mucosae-associated epithelial chemokine (MEC) fractalkine, inhibited a inhibitor. higher IBD than control dogs. significantly elevated IBD, level correlated positively clinical severity score. These results suggest that may contribute pathogenesis inducing mediators response luminal proteases.