Stimulation of human T-cells by pokeweed mitogen (PWM) results in a significant increase of IL-2, IFN-gamma, and DP IV mRNA expression as analyzed by quantitative RT-PCR. Here we show for the first time that the changes observed in cytokine mRNA expression are dose-dependently suppressed by the specific dipeptidyl peptidase IV inhibitor Lys[Z(NO(2))]-thiazolidide. Most interestingly, the inhibition of DP IV activity leads to a decrease in mRNA expression of the enzyme itself. Furthermore, evidence is provided that this suppression is mediated by TGF-beta(1). The presented data fit into the hypothesis that inhibition of DP IV leads to the induction of TGF-beta(1), which in turn provokes an arrest of cell cycle in late G(1).
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