Inflammatory bowel diseases: multiple benefits from therapy with dipeptidyl- and alanyl-aminopeptidase inhibitors

Abstract

Inflammatory bowel diseases (IBD) are driven by imbalances in innate and acquired immune response. In IBD two dysregulated T cell subsets are in the focus of interest: activated effector T cells and regulatory T cells. These T cell subsets are characterized by a strong expression of the ectopeptidases dipeptidyl peptidase IV (DPIV /CD26) and aminopeptidase N (APN/CD13), which are thought to a role in the control of immune activation and in regulating cellular communication by hydrolyzing bioactive polypeptides. Since inhibitors of both enzymes were shown to be effective in limiting immune activation processes in vitro as well as in vivo, they emerged as new drug candidates for the treatment of diseases associated with an imbalanced T cell response, such as IBD. In this review we intent to throw light on the putative role of DPIV, APN and related enzymes in the regulation of immune and non-immune processes in inflammatory bowel diseases, on possible benefits from peptidase inhibitor therapy in these diseases as well on the gaps of knowledge in this field.

Effect of divalent cations on the porcine kidney cortex membrane-bound form of dipeptidyl peptidase IV

“…Changes in zinc homeostasis, in particular a deficiency of this ion, appear to be associated with diseases like hepatic cirrhosis, head, neck or prostate cancer, bowel disease, as well as with impaired function of the immune system (Reviewed in Jansen et al, 2009). Interestingly, in several of these pathologies, a high activity of DPP-IV is implicated (Bank et al, 2008;Wilson et al, 2005;Yazbeck et al, 2009;Yilmaz et al, 2009). However, no previous report correlates an elevated activity of this enzyme with concentrations of plasma zinc below normal values.…”

Development and resolution of colitis in mice with target deletion of dipeptidyl peptidase IV

“…Apart from its enzymatic activity, its expression defines a T-helper (Th)1/Th0 phenotype among T cells and correlates with enhanced production of Th1-like cytokines. In addition, DPP IV/CD26 inhibitors have been shown to be effective in limiting immune activation processes and to modify the course of disease associated with an imbalanced T cell response, as in IBD (Bank et al , 2008Reinhold et al 2006;Yazbeck et al 2008).…”

Dipeptidyl Peptidase IV in Inflammatory Bowel Diseases (DPP IV/CD26)

“…Međutim unatoč različitoj imunosnoj pozadini pojedinog entiteta upalnih bolesti crijeva, serumska aktivnost DPP IV/CD26 nije se pokazala dobrim markerom za dijagnostičko razlikovanje CB-a i UK (9). No unatoč brojnim istraživanjima uloga ove molekule u patogenezi UBC-a, kao i drugim kroničnim upalnim bolestima, ostaje nerazjašnjena (115).…”