engleski

Neuroimmunomodulation mediated by DPP IV/CD26 in murine experimental colitis

Dipeptidyl peptidase IV (DPP IV/CD26) is a multifunctional protein and serine protease which plays crucial roles in physiological and pathological conditions. Neuropeptide Y (NPY) is considered to have a role in the regulation of immune and inflammatory events. Vasoactive intestinal peptide (VIP) has potential protective effect on intestinal mucosa. Both VIP and NPY are gut-brain peptides and DPP IV substrates. A causal connection between DPP IV/CD26 and inflammatory events has been proposed but mechanisms of this interactions are still unclear. Our hypothesis was that DPP IV/CD26 could affect the neuroimmune response at the systemic and local levels during colitis development and resolution in mice. Our aim was to evaluate the possible role of DPP IV/CD26 and the relevance of the gut-brain axis in a colitis model in mice. A model of Crohn’s disease has been induced in CD26 deficient and wild type (C57BL/6) mice using 2, 4, 6-trinitrobenzenesulfonic acid (TNBS). Experimental animals were monitored daily and sacrified on crucial days of colitis. NPY and VIP concentrations and protein expressions likewise DPP IV/CD26 enzymatic activity have been determined among the gut-brain axis, on local and systemic levels, by ELISA and Western blot techniques. Our study revealed constitutionally significantly (p<0.05) higher serum VIP concentrations in CD26 deficient compared to wild-type mice. Maximum values were determined in the acute phase of colitis in serum, colon and brain. NPY concentrations in the colon were increased in both mice strains in acute inflammation as well, with significantly (p<0.05) higher values in CD26 deficient mice. DPP IV/CD26 enzymatic activities among the gut-brain axis was also found to be altered in the acute phase of the disease. Obtained results indicate a causal connection between levels of VIP and NPY, inflammatory events and the activity of DPP IV/CD26. The relevance off the gut-brain axis has been confirmed. DPP IV/CD26 has been shown to play an important neuroimmunomodulative role in colitis pathogenesis and should be further evaluated in order to develop new potential therapeutical approaches.

Colitis ; Colon ; Neuroimmunomodulation ; Neuropeptide ; Trinitrobenzenesulfonic Acid

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