engleski

Impact of DPP IV/CD26 Deficiency on Neuropeptide Y among the Gut-brain Axis in Experimental Colitis

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract with unclear etiology. A bidirectional connection between central and enteric nervous systems and the role of peptidases in maintaining the homeostasis in the gut via bioactive substrates has been proposed. Dipeptidyl-peptidase IV (DPP IV/CD26), a multifunctional glycoprotein found in soluble and membrane-bound form, whose role in immune-mediated diseases was described. The involvement of neuropeptide Y (NPY), a substrate of DPP IV/CD26, in experimental colitis has been indicated. Our hypothesis was that DPP IV/CD26 plays an important role in IBD by influencing the circulating and tissue levels of NPY in an experimental model of IBD. In order to evaluate the impact of DPP IV/CD26 on NPY levels among the gut-brain axis, a Crohn-like model of colitis has been induced in CD26 deficient and wild type (C57BL/6) mice. Decreased DPP IV/CD26 activity was found in serum, colon and brain in wild type mice with colitis, while CD26 expression was increased in colon. Inflammatory events in the colon lead to an increase in serum and colon NPY concentrations in both mice strains. Serum NPY changes were more emphasized in CD26 deficient mice, while NPY colon concentration was higher in wild type. Furthermore, we determined that colitis induces an increase in brain NPY concentration in the acute phase in wild type mice and, adversely, a decrease in CD26 deficient mice. Results of this study have shown that changes occurring during inflammatory processes in colon reflected on investigated parameters in brain. Our results indicate the importance of the gut-brain axis in the pathogenesis of IBD, as well as an important impact of DPP IV/CD26 on NPY during experimental colitis.

DPP IV/CD26; NPY; gut-brain axis; experimental colitis

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