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

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. [ABSTRACT FROM AUTHOR]