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CD26 deficiency alters VIP and NPY levels in murine Crohn-like colitis

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions that affect different parts of the gastrointestinal tract. The etiology of IBD is unclear, but increasing scientific evidence confirms a bidirectional connection between central and enteric nervous system, known as gut-brain axis. In this context, peptidases exert a key role in maintaining the homeostasis in the gut by regulating the biological activity of their bioactive substrates at local, circulating and central level. Dipeptidylpeptidase IV (DPP IV/CD26) is a pleiotropic membrane glycoprotein found also in soluble form in different biological fluids, associated with important processes in the organism, both in physiological and pathological conditions. Neuropeptide Y (NPY) and Vasoactive intestinal peptide (VIP) are substrates of DPP IV/CD26, which involvement in chronic inflammatory processes, including IBD, has been indicated. Our hypothesis was that DPP IV/CD26 plays an important neuroimmunomodulatory role in IBD pathogenesis by influencing circulating and tissue levels of NPY and VIP in a chemicallyinduced model of colitis in mice. In order to evaluate the impact of DPP IV/CD26 on NPY and VIP levels among the gut- brain axis, a trinitrobenzenesulfonic acid (TNBS-induced ; Crohn-like) model of colitis has been induced in CD26 deficient (CD26-/-) and wild type (C57BL/6) mice. NPY and VIP concentrations and protein expressions have been determined at both systemic and local levels. Results of our study showed that VIP concentrations and protein expressions in serum, colon and brain of both mice strains reach their maximum values in the acute phase of colitis, but the increment was more pronounced in CD26-/- mice (p<0.05). The increase of serum NPY concentration was more emphasized in CD26-/- mice, while NPY colon concentration and protein expression was higher in C57BL/6 mice. Furthermore, colon inflammation induced an increase in brain NPY concentration in the acute phase in C57BL/6 mice and, adversely, a decrease in CD26-/- mice. 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 VIP and NPY levels during experimental colitis.

Dipeptidyl-peptidase IV (DPP IV/CD26); vasoactive intestinal peptide; inflammatory bowel disease.

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