Dipeptidyl peptidase IV (DP IV/CD26) mRNA expression in PWM-stimulated T-cells is suppressed by specific DP IV inhibition, an effect mediated by TGF-beta(1).
Stimulation of human T-cells by pokeweed mitogen (PWM) results in a significant increase of IL-2, IFN-gamma, and DP IV mRNA expression as analyzed by quantitative RT-PCR. Here we show for the first time that the changes observed in cytokine mRNA expression are dose-dependently suppressed by the specific dipeptidyl peptidase IV inhibitor Lys[Z(NO(2))]-thiazolidide. Most interestingly, the inhibition of DP IV activity leads to a decrease in mRNA expression of the enzyme itself. Furthermore, evidence is provided that this suppression is mediated by TGF-beta(1). The presented data fit into the hypothesis that inhibition of DP IV leads to the induction of TGF-beta(1), which in turn provokes an arrest of cell cycle in late G(1).
Arndt
M
M
Institute of Immunology, Centre of Internal Medicine, Otto von Guericke University, Leipziger Strasse 44, Magdeburg, D-39120, Germany.marco.arndt@medizin.uni-magdeburg.de
Lendeckel
U
U
Spiess
A
A
Faust
J
J
Neubert
K
K
Reinhold
D
D
Ansorge
S
S
D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D000906:Antibodies; D007376:Interleukin-2; D011043:Pokeweed Mitogens; D011480:Protease Inhibitors; D012333:RNA, Messenger; D013844:Thiazoles; D016212:Transforming Growth Factor beta; C093632:lysyl-(Z(nitro))thiazolidide; D007371:Interferon-gamma; D018819:Dipeptidyl Peptidase 4; D008239:Lysine