engleski

Dipeptidyl peptidase IV affects neruopeptide Y levels in inflammatory events

Proteases have been proposed as one of the key factors in the occurrence of inflammatory processes due to their ability to metabolize different biologically active molecules implicated in inflammatory events. Dipeptidyl peptidase IV (DPP IV/CD26), a multifunctional glycoprotein found in both soluble and membrane-bound form, regulates circulating bioactive peptides and participates in the modulation of the immune response through its enzymatic function and expression on various immune cells. Neuropeptide Y (NPY), a substrate of DPP IV/CD26, is produced by central and peripheral nervous system as well as by immune cells and has pleiotropic effects on both innate and adaptive immune system. Truncation alliterates the affinity of NPY to its receptors and the relevance of the DPP IV/CD26 - NPY connection in autoimmune and inflammatory diseases has been indicated. We hypothesized that DPP IV/CD26 through its neuroimmunomodulative properties plays an important role in rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD). Since clinical studies suggested the importance of DPP IV/CD26 and NPY in autoimmunity, we investigated their systemic and local levels in adult patients affected with RA and osteoarthritis, latter representing a control group. Activity and concentration of DPP IV/CD26 were significantly decreased in both synovial fluid and serum, while, inversely, immunodetection showed elevated levels of NPY. Furthermore, our previous studies showed altered concentration of DPP IV/CD26 in serum of IBD patients, hence our research was broaden to an experimental model of IBD in order to investigate the effects of DPP IV/CD26 deficiency on the circulating and tissue levels of NPY in CD26 deficient and wild-type mice with induced colitis. During colitis development, decreased DPP IV/CD26 activity was found in serum, colon and brain in wild type mice, while CD26 expression was increased in colon. Inflammatory events in the colon lead to an increase in serum and colon NPY concentrations in both mice strains. Colitis induced an increase in brain NPY concentration in the acute phase in wild type mice and, adversely, a decrease in CD26 deficient mice. In conclusion, mechanisms activated upon inflammation induce changes in NPY secretion systemically and at the sites of inflammation, in both IBD and RA, which further confirms the impact of DPP IV/CD26 on its bioactive substrate NPY in chronic autoimmune disorders.

Dipeptidyl peptidase IV (DPP IV); Inflammatory bowel disease; Neuropeptide Y; Rheumatoid arthritis

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