Inhibitors of dipeptidyl peptidase iv induce secretion of transforming growth factor-β1 in PWM-stimulated PBMC and T cells

Abstract

Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV (DP IV; CD26), expressed on T, natural killer (NK) and B cells in the immune system, is involved in the regulation of DNA synthesis and cytokine production. We show that the specific DP IV inhibitors Lys[Z(NO2)]-thiazolidide, Lys[Z(NO2)]-piperidide, and Lys[Z(NO2)]-pyrrolidide inhibit DNA synthesis as well as production of interleukin-2 (IL-2 ), IL-10, IL-12, and interferon-γ, (IFN-γ) of pokeweed mitogen (PWM)- stimulated purified T cells. Most importantly, these inhibitors induce a three- to fourfold increased secretion of latent transforming growth factor-β1 (TGF-β1) by PWM-stimulated peripheral blood mononuclear cells (PBMC) and T cells. as measured with a specific TGF-β1 enzyme-linked immunosorbent assay and in the Mv1Lu bioassay. As we could demonstrate previously, TGF-β1 exhibits the same inhibitory effects as DP IV inhibitors on DNA synthesis and cytokine production (Cytokine 1994, 6, 382 8: J Interferon Cytokine Res 1995, 15. 685-90). A neutralizing chicken anti-TGF-β1 antibody was capable of abolishing the DP IV inhibitor-induced suppression of DNA synthesis of PWM-stimulated PBMC and T cells. These data suggest that TGF-β1 might have key functions in the molecular action of DP IV/CD26 in regulation of DNA synthesis and cytokine production.