Inhibitors of dipeptidyl peptidase IV induce secretion of transforming growth factor-beta 1 in PWM-stimulated PBMC and T cells.
Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV (DP IV; CD26), expressed on T, natural killer (NK) and B cells in the immune system, is involved in the regulation of DNA synthesis and cytokine production. We show that the specific DP IV inhibitors Lys[Z(NO2)]-thiazolidide, Lys[Z(NO2)]-piperidide, and Lys[Z(NO2)]-pyrrolidide inhibit DNA synthesis as well as production of interleukin-2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-gamma) of pokeweed mitogen (PWM)-stimulated purified T cells. Most importantly, these inhibitors induce a three- to fourfold increased secretion of latent transforming growth factor-beta 1 (TGF-beta 1) by PWM-stimulated peripheral blood mononuclear cells (PBMC) and T cells, as measured with a specific TGF-beta 1 enzyme-linked immunosorbent assay and in the Mv1Lu bioassay. As we could demonstrate previously, TGF-beta 1 exhibits the same inhibitory effects as DP IV inhibitors on DNA synthesis and cytokine production (Cytokine 1994, 6, 382-8; J Interferon Cytokine Res 1995, 15, 685-90). A neutralizing chicken anti-TGF-beta 1 antibody was capable of abolishing the DP IV inhibitor-induced suppression of DNA synthesis of PWM-stimulated PBMC and T cells. These data suggest that TGF-beta 1 might have key functions in the molecular action of DP IV/CD26 in regulation of DNA synthesis and cytokine production.
Reinhold
D
D
Department of Internal Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
Bank
U
U
Bühling
F
F
Lendeckel
U
U
Faust
J
J
Neubert
K
K
Ansorge
S
S
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011043:Pokeweed Mitogens / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D011043:Pokeweed Mitogens; D011480:Protease Inhibitors; D016212:Transforming Growth Factor beta; D004247:DNA; D018819:Dipeptidyl Peptidase 4