engleski

THE CONCENTRATION OF VASOACTIVE INTESTINAL PEPTIDE IS ALTERED BY DIPEPTIDYL PEPTIDASE IV DEFICIENCY AMONG THE GUT-BRAIN AXIS IN EXPERIMENTAL COLITIS

Introduction Inflammatory bowel disease (IBD) describes a chronic inflammatory disorder of the gastrointestinal tract including Crohn’s disease and ulcerative colitis. Dipeptidyl-peptidase IV (DPP IV/CD26) is a membrane-bound and soluble glycoprotein, showing a pleiotropic role in the organism. We hypothesized that DPP IV/CD26 contributes to the pathogenesis of IBD by influencing circulating and tissue levels of its substrate, vasoactive intestinal peptide (VIP), along the gut-brain axis (serum, colon and brain tissue). Materials and methods A 2, 4, 6- trinitrobenzenesulfonic acid (TNBS)- induced Crohn-like model of colitis has been induced in CD26 deficient and wild-type (C57BL/6) mice. Control animals received the same volume of 50% ethanol and saline solution (6-8 animals per group). Animals were monitored daily and sacrificed 2, 7, 10, 15, and 30 days after TNBS application. Histomorphometric and pathohistological analyses of colon tissues were performed. VIP concentrations and protein expressions as well as DPP IV/CD26 enzymatic activity along the gut-brain axis have been determined at both systemic and local levels by ELISA and Western blot techniques. Results: This study revealed that CD26 deficient mice constitutionally have significantly higher serum VIP concentrations compared to their wild- type counterparts. VIP concentrations in serum of both mice strains reach their maximum values in the acute phase of colitis, significantly more accentuated in CD26 deficient mice. Likewise, VIP levels in the brain showed increased concentrations in both mice strains in acute inflammation with significantly higher values in CD26 deficient mice. Discussion/Conclusion Results of this study indicate that mechanisms activated locally in the gut mucosa upon inflammatory events induce changes in neuropeptides in the brain, thereby, confirming the importance of the gut- brain axis in IBD. In addition, DPP IV/CD26 has been confirmed to play an important neuroimmunomodulatory role in IBD pathogenesis, which should further be evaluated.

Brain-gut axis, Vasoactive intestinal peptide, DPP IV/CD26

Nagrada za najbolje postersko izglaganje i stipendija za 1 mjesec istraživačkog rada u Švicarskoj, Basel, laboratorij prof. Probstel