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

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Abstract
Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV (DPIV; 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.