Involvement of DPP IV/CD26 in cutaneous wound healing process in mice.

Dipeptidyl peptidase IV (DPP IV/CD26) is a widely distributed multifunctional protein that plays a significant role in different physiological as well as pathological processes having a broad spectrum of bioactive substrates and immunomodulative properties. It has potential influence on different processes crucial for wound healing, including cell adhesion, migration, apoptosis, and extracellular matrix degradation. However, despite its known enzymatic and immunomodulative functions, limited data characterize the role of DPP IV/CD26 in cutaneous wound healing mechanisms. The aim of this study was to investigate the process of wound healing in conditions of CD26 deficiency in order to obtain better insights on the role of DPP IV/CD26 in cutaneous regeneration. Experimental wounds were made on the dorsal part of CD26 deficient (CD26-/- ) and wild-type mice (C57BL/6). The process of cutaneous wound healing was monitored on defined time schedule postwounding by macroscopic, microscopic, and biochemical analyses. Obtained results revealed a better rate of wound closure, revascularization and cell proliferation in CD26-/- mice, with enhanced local expression of hypoxia-inducible factor 1α and vascular endothelial growth factor. CD26 deficiency induced prompt macrophage recruitment at the site of skin damage but did not influence mobilization of T-cells in comparison with wild-type mice. CD26-/- mice have significantly higher values of IP-10 in serum and control skins compared with wild-type mice but values in wounds did not differ significantly on days 2, 4, and 7 of wound healing. DPP IV/CD26 activity was found to be decreased 4 days postwounding in serum and 2, 4, and 7 days postwounding in wounds of wild-type animals compared with control skins. These findings contribute to better understanding of wound healing mechanisms and could give a support in finding new therapeutic approaches for wound healing and tissue regeneration.

Influence of CD26/dipeptidyl peptidase IV deficiency on immunophenotypic changes during colitis development and resolution

A lot of evidence for the importance of CD26/dipeptidyl peptidase IV (CD26/DPP IV) in immunoactivation has been reported; however, its involvement in colitis remains unclear. The aim of this study was to investigate the influence of CD26/DPP IV deficiency on immunophenotypic changes associated with dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) and CD26-deficient mice. Development of clinical symptoms of colitis and animal health status parameters were assessed; the expression of the nuclear factor (NF)-κB p65 subunit was measured by quantitative real-time PCR, while cell characterization was determined by flow cytometry and immunohistochemical staining. DSS treatment induced loss of body weight and colon length shortening in both mouse strains. An increase of myeloperoxidase activity in CD26-deficient mice was more intensive than in WT mice, in spite of similar histopathological changes. Furthermore, a significant increase in the expression of NF-κB p65 subunit in the colon of CD26-deficient mice was determined. The percentage of splenic CD4+ and CD8+ cells in the acute phase of colitis was significantly decreased in WT mice, while in the same period, an increase in the percentage of splenic CD8+ cells was present in CD26-deficient mice. Development of colitis was accompanied by a significant increase in the percentage of intrahepatic NKT cells in both mouse strains, but their percentage in spleen was increased only in CD26-deficient mice. CD26 deficiency was associated with a heightened response to DSS accompanied by increased expression of NF-κB p65 subunit and distinct changes in leukocyte trafficking. These results provide new insights into the role of CD26/DPP IV during the development of colitis (AU)

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