Inhibitors of dipeptidyl peptidase IV (DP IV, CD26) induces secretion of transforming growth factor-beta 1 (TGF-beta 1) in stimulated mouse splenocytes and thymocytes.
Various studies have shown that the ectoenzyme dipeptidyl peptidase IV (DP IV, CD26), expressed on T, NK and B cells in the human immune system, is involved in the regulation of DNA synthesis and cytokine production. The DP IV/CD26 was found also on mouse splenocytes and thymocytes. Here, we show that the specific DP IV inhibitors Lys[Z(NO2)]-thiazolidide, Lys[Z(NO2)]-pyrrolidide inhibit DNA synthesis as well as production of IL-2, IL-6 and IL-10 of PHA-stimulated mouse splenocytes and Con A-stimulated mouse thymocytes. Most importantly, these inhibitors induce a three to fourfold increased secretion of latent transforming growth factor beta 1 (TGF-beta 1) by mitogen-stimulated mouse immune cells, as measured with a specific TGF-beta 1 enzyme-linked immunosorbent assay (ELISA). These data demonstrate that CD26 plays a role also in regulation of DNA synthesis and cytokine production by murine immune cells, that the enzymatic activity is required for mediating these effects, and that TGF-beta 1 might have key functions in these processes.
Reinhold
D
D
Department of Internal Medicine, Otto-von-Guericke-University Magdeburg, Germany.
Bank
U
U
Bühling
F
F
Täger
M
M
Born
I
I
Faust
J
J
Neubert
K
K
Ansorge
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D007378:Interleukins / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011480:Protease Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D007378:Interleukins; D011480:Protease Inhibitors; D011759:Pyrrolidines; D013844:Thiazoles; D016212:Transforming Growth Factor beta; C110164:lysyl-(Z(nitro))pyrrolidide; C093632:lysyl-(Z(nitro))thiazolidide; D018819:Dipeptidyl Peptidase 4; D008239:Lysine