DNA synthesis in cultured human keratinocytes and HaCaT keratinocytes is reduced by specific inhibition of dipeptidyl peptidase IV (CD26) enzymatic activity.
The ectopeptidase dipeptidyl peptidase IV (DP IV, CD26, EC 3.4.14.5) is present on most mammalian cells. Using specific inhibitors of DP IV, it has been shown that this enzyme is involved in the regulation of DNA synthesis and in production of various cytokines in lymphocytes. The aim of the present work was to investigate the expression of DP IV/CD26 on human keratinocytes and to answer the question, whether the proliferation (DNA synthesis) of human keratinocytes is influenced by inhibition of the enzymatic activity of DP IV. Using flow cytometry, RT-PCR, and specific enzymatic activity assays, expression of DP IV-mRNA and CD26 antigen were shown on primary keratinocyte strains and on the HaCaT keratinocyte cell line. The synthetic DP IV inhibitors Lys[Z(NO2)]-thiazolidide and -pyrrolidide suppress the DNA-synthesis of these cells in a dose-dependent manner. These data demonstrate that CD26 is also involved in the regulation of DNA synthesis of keratinocytes and that the enzymatic activity is required for mediating these effects.
Vetter
R
R
Dept. of Dermatology and Venereology, Otto-von-Guericke University, Germany.
Reinhold
D
D
Bühling
F
F
Lendeckel
U
U
Born
I
I
Faust
J
J
Neubert
K
K
Ansorge
S
S
Gollnick
H
H
D000328:Adult; D002460:Cell Line / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D011759:Pyrrolidines; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; C110164:lysyl-(Z(nitro))pyrrolidide; C093632:lysyl-(Z(nitro))thiazolidide; D018819:Dipeptidyl Peptidase 4; D008239:Lysine