INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DP-IV, CD26) INDUCES SECRETIONOF TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) IN STIMULATED MOUSESPLENOCYTES AND THYMOCYTES

Various studies have shown that the ectoenzyme dipeptidyl peptidase IV (DP IV, CD26), expressed on T, NK and B cells in the human immune sys tem, is involved in the regulation of DNA synthesis and cytokine produ ction. The DP IV/CD26 was found also on mouse splenocytes and thymocyt es. Here, we show that the specific DP IV inhibitors Lys[Z(NO2)]-thiaz olidide; Lys[Z(NO2)]-pyrrolidide inhibit DNA synthesis as well as prod uction of IL-2, IL-6 and IL-10 of PHA-stimulated mouse splenocytes and Con A-stimulated mouse thymocytes. Most importantly, these inhibitors induce a three to fourfold increased secretion of latent transforming growth factor beta 1 (TGF-beta 1) by mitogen-stimulated mouse immune cells, as measured with a specific TGF-beta 1 enzyme-linked immunosorb ent assay (ELISA). These data demonstrate that CD26 plays a role also in regulation of DNA synthesis and cytokine production by murine immun e cells, that the enzymatic activity is required for mediating these e ffects, and that TGF-beta 1 might have key functions in these processe s. (C) 1997 Elsevier Science B.V.