Interferon-gamma induces dipeptidylpeptidase IV expression in human glomerular epithelial cells.
Because dipeptidylpeptidase IV (DPP IV) is present in vivo on glomerular 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 product of the reaction in the incubation medium of intact cells and the staining of paraformaldehyde-fixed cells in the presence of a specific anti-DPP IV antibody. DPP IV activity was inhibited by diisopropylfluorophosphate and phenylmethyl sulphonylfluoride. Its optimum pH was alkaline (7.7-8) and it exhibited a Km value of 0.94 mM. DPP IV expression was induced in cells treated by interferon-gamma (IFN-gamma). The effect was significant after a 3-day treatment with 100 U/ml. It increased 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 was 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 inefficient. These results suggest that DPP IV of glomerular epithelial cells may be up-regulated by IFN-gamma from activated T lymphocytes in glomerular diseases and during lymphocyte-mediated graft rejection.
Stefanovic
V
V
INSERM 64, Hôpital Tenon, Paris, France.
Ardaillou
N
N
Vlahovic
P
P
Placier
S
S
Ronco
P
P
Ardaillou
R
R
D015152:Blotting, Northern; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000201:enzymology / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins
D011480:Protease Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4