INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DP-IV, CD26) SPECIFICALLY SUPPRESS PROLIFERATION AND MODULATE CYTOKINE PRODUCTION OF STRONGLY CD26 EXPRESSING U937 CELLS

Various studies from different laboratories have shown that the membra ne ectoenzyme dipeptidyl pepridase IV (DP IV, CD26) expressed in T and NK cells is involved in the regulation of DNA synthesis and cytokine production. In this paper, we performed a biochemical and functional c haracterization of dipeptidyl peptidase IV on the human histiocytic ly mphoma cell line U937. Using U937 clones expressing low to high levels of membrane localized CD26, we found that the synthetic reversible in hibitors of DP IV, Lys-[Z(NO2)]-thiazolidide and Lys-[Z(NO2)]-piperidi de, have different effects on all functions. In U937-H cells that stro ngly express high levels of CD26, DP IV inhibitors were shown to suppr ess DNA synthesis and production of IL-1 beta, but stimulate the secre tion of the IL-1 receptor antagonist (IL-1RA) and of TNF-alpha. In con trast, both inhibitors did not influence the cytokine production and D NA synthesis in U937-L cells exhibiting low level CD26 expression. The se data support the hypothesis that CD26 plays a crucial role in proli feration and cytokine production, not only in T cells, but also in oth er cell systems, and that enzymatic activity is essential for its func tion.