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Inhibitors of dipeptidyl peptidase IV induce secretion of transforming growth factor‐ β 1 in PWM‐stimulated PBMC and T cells
Author(s) -
REINHOLD D.,
BANK U.,
BÜHLING F.,
LENDECKEL U.,
FAUST J.,
NEUBERT K.,
ANSORGE S.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.d01-2258.x
Subject(s) - dipeptidyl peptidase , secretion , peripheral blood mononuclear cell , transforming growth factor , growth factor , microbiology and biotechnology , biology , cancer research , endocrinology , biochemistry , enzyme , receptor , in vitro
Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV (DPIV; 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(NO 2 )]‐thiazolidide, Lys[Z(NO 2 )]‐piperidide, and Lys[Z(NO 2 )]‐pyrrolidide inhibit DNA synthesis as well as production of interleukin‐2 (IL‐2), IL‐10, IL‐12, and interferon‐ γ (IFN‐ γ ) of pokeweed mitogen (PWM)‐stimulated purified T cells. Most importantly, these inhibitors induce a three‐ to fourfold increased secretion of latent transforming growth factor‐ β 1 (TGF‐ β 1 ) by PWM‐stimulated peripheral blood mononuclear cells (PBMC) and T cells, as measured with a specific TGF‐ β 1 enzyme‐linked immunosorbent assay and in the Mv1Lu bioassay. As we could demonstrate previously, TGF‐ β 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‐ β 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‐ β 1 might have key functions in the molecular action of DP IV/CD26 in regulation of DNA synthesis and cytokine production.