Specific inhibitors of dipeptidyl peptidase IV suppress mRNA expression of DP IV/CD26 and cytokines.
The dipeptidyl peptidase IV is an activation marker on T, B and NK cells. Specific inhibitors of DP IV suppress DNA synthesis, as well as cytokine protein production. Here, we describe for the first time the quantitative changes of mRNA expression of IFN-gamma, IL-2, IL-12 and DP IV after inhibition of DP IV. Due to the stimulation of human peripheral blood mononuclear cells (PBMC) with pokeweed mitogen (PWM) both cytokine as well as DP IV mRNA expression is increased significantly. Treatment with DP IV inhibitor suppresses dose-dependently these changes. Importantly, mRNA expression of DP IV itself was inhibited. The presented data are fully compatible with our hypothesis that inhibition of DP IV leads to cell cycle arrest in late G1 due to enhanced TGF-beta 1 expression.
Arndt
M
M
Institute of Immunology, Center of Internal Medicine, Otto von Guericke University Magdeburg, Germany.
Reinhold
D
D
Lendeckel
U
U
Spiess
A
A
Faust
J
J
Neubert
K
K
Ansorge
S
S
D019898:Autocrine Communication; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D005246:Feedback; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D053773:Transforming Growth Factor beta1
D007376:Interleukin-2; D011043:Pokeweed Mitogens; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; C508960:TGFB1 protein, human; D013844:Thiazoles; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C093632:lysyl-(Z(nitro))thiazolidide; D018664:Interleukin-12; D007371:Interferon-gamma; D018819:Dipeptidyl Peptidase 4; D008239:Lysine