INTERFERON-GAMMA INDUCES DIPEPTIDYLPEPTIDASE-IV EXPRESSION IN HUMAN GLOMERULAR EPITHELIAL-CELLS

Because dipeptidylpeptidase IV (DPP IV) is present in vivo on glomerul ar visceral epithelial cells and possesses immunogenic properties, as shown by the capability of anti-DPP IV antibody to induce the Heymann model of glomerulonephritis, we studied the expression and regulation of DPP IV in cultured human glomerular visceral epithelial cells. DPP IV is an ectoenzyme, as indicated by the rapid detection of the produc t of the reaction in the incubation medium of intact cells and the sta ining of paraformaldehyde-fixed cells in the presence of a specific an ti-DPP IV antibody. DPP IV activity was inhibited by diisopropylfluoro phosphate and phenylmethyl sulphonylfluoride. Its optimum pH was alkal ine (7.7-8) and it exhibited a K(m) value of 0.94 mm. DPP IV expressio n was induced in cells treated by interferon-gamma (IFN-gamma). The ef fect was significant after a 3-day treatment with 100 U/ml. It increas ed with time, reaching a plateau after 11 days, and was dose-dependent with a maximum at a concentration of 1000 U/ml. Staining of the cells with anti-DPP IV antibody was also increased after a 6-day treatment with 100 U/ml IFN-gamma. It was shown by Northern analysis that, after 24 hr of exposure to 500 U/ml of IFN-gamma, DPP IV mRNA transcript wa s stimulated. Transcriptional activation by IFN-gamma did not require new protein synthesis. Interleukin-1 (IL-1) and cyclic AMP had a small stimulatory effect, whereas dexamethasone and phorbol esters were ine fficient. These results suggest that DPP IV of glomerular epithelial c ells may be up-regulated by IFN-gamma from activated T lymphocytes in glomerular diseases and during lymphocyte-mediated graft rejection.