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Could vasoactive intestinal peptide be a VIP substrate of dipeptidyl peptidase IV (DPP IV/CD26) involved in experimental murine colitis?

Dipeptidyl peptidase IV (DPP IV/CD26) is a membrane-bound glycoprotein expressed on different cell types, having multiple functions in various biological processes, including immunological regulations. A soluble form circulating in body fluids is found in living organisms. As a serine protease, it possesses a specific peptidase function with unique features in substrate processing. Different cytokines, chemokines and neuropeptides involved in inflammatory events are found among DPP IV/CD26 substrates. One of them is Vasoactive intestinal peptide (VIP), a neuropeptide with growing evidence of involvement in inflammatory processes and wound healing. The aim of this study was to determine serum VIP concentrations in different periods of time after induction of colitis in mice by trinitrobenzensulfonic acid (TNBS). In order to examine the role of DPP IV/CD26 in VIP metabolism during experimental colitis, wild type mice and CD26 deficient mice were used. The results of this study indicated that CD26 deficient mice have statistically significantly higher serum VIP concentrations in physiological conditions compared to wild type mice. The second day following TNBS administration, which represents the acute phase of disease, is characterized by a statistically significant increase in serum VIP concentrations in both mice groups, with more accentuated increase in CD26 deficient group of mice. Serum VIP concentrations start to decrease the seventh day, continue to decrease during the fifteenth day and finally reach physiological concentrations the thirtieth day following TNBS administration. It was determined that serum VIP concentrations correlate with inflammatory occurrences in experimental murine colitis. Thus, it can be concluded that DPP IV/CD26 plays a significant role in VIP metabolism and therefore has a potential modulatory effect on the immunological response in inflammatory events.

dipeptidyl-peptidase IV; CD26 molecule; vasoactive intestinal peptide; experimental colitis; mice; CD26 deficiency

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