engleski

Deficiency of DPP IV/CD26 Impacts Vasoactive Intestinal Peptide Levels among the Gut-brain Axis in Acute Inflammation

Inflammatory bowel disease (IBD, including Crohn's disease and ulcerative colitis), is a group of chronic inflammatory conditions of the gastrointestinal tract with unclear etiology. Increasing scientific evidence confirms a bidirectional connection between central and enteric nervous systems, where peptidases exert a key role in maintaining the homeostasis in the gut via their bioactive substrates. Dipeptidyl- peptidase IV (DPP IV/CD26) is an intrinsic membrane glycoprotein found also in soluble form in biological fluids, associated with different important processes, including immune regulation. Vasoactive intestinal peptide (VIP) is an important substrate of DPP IV/CD26, which involvement in chronic inflammatory processes, including IBD, has been proven. Our hypothesis was that DPP IV/CD26 plays an important role in IBD pathogenesis by influencing circulating and tissue levels of VIP in a chemically-induced model of IBD in mice. In order to evaluate the effect of DPP IV/CD26 on VIP levels among the gut-brain axis, a trinitrobenzenesulfonic acid (TNBS)-induced (Crohn-like) model of colitis has been induced in CD26 deficient and wild type mice. Results of our study showed that CD26 deficient mice constitutionally have statistically significantly (p<0.05) higher serum VIP concentrations compared to C57BL/6 mice. VIP concentrations in serum of both mice strains reach their maximum values in the acute phase of colitis, but the increment is more pronounced in CD26 deficient mice. VIP concentrations in colon were also increased in both mice strains in acute inflammation, with statistically significantly (p<0.05) higher values in CD26 deficient mice. Changes at the local site of inflammation influenced VIP levels in the brain, also showing increased concentrations in both mice strains in acute inflammation with statistically significantly (p<0.05) higher values in CD26 deficient mice. Our results indicate and prove the importance of the gut-brain axis in the pathogenesis of IBD as well as an important impact of DPP IV/CD26 on its bioactive substrate VIP during experimental colitis.

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

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