CD26 mediates the action of HIV-1 Tat protein on DNA synthesis and cytokine production in U937 cells.
The human immunodeficiency virus 1 (HIV-1) Tat protein is known to be capable of suppressing antigen- and CD3-induced activation of human T cells. Previously, it was shown that Tat can bind to the dipeptidyl peptidase IV (DP IV, CD26) and inhibit the degradation of the chromogenic substrate Gly-Pro-p-nitroanilide. Using the method of free zone capillary electrophoresis, here we have shown that the DP IV-catalyzed hydrolysis of the NH2-X-Pro-containing cytokine peptides IL-2(1-12), IL-1 beta(1-6), and IL-6(1-12) was also significantly inhibited by the Tat protein. Moreover, HIV-1 Tat at a concentration of 10 micrograms/ml was found to have a strong suppressive effect on DNA synthesis and IL-1 beta production, but stimulates secretion of IL-1 receptor antagonist (IL-1RA) and TNF-alpha of CD26-expressing U937-H cells. It did not impair neither DNA synthesis nor cytokine production of low CD26-expressing U937-L cells. Similar results have been found with synthetic DP IV/CD26 inhibitors (Immunobiol., 1994, vol. 192, pp. 121-136). These data strongly suggest that Tat protein is a potent "natural" inhibitor of DP IV/CD26, and they support the hypothesis that DPIV plays a role in Tat's immunosuppressive activity.
Reinhold
D
D
Department of Internal Medicine, Otto von Guericke University, Magdeburg.
Wrenger
S
S
Bank
U
U
Bühling
F
F
Hoffmann
T
T
Neubert
K
K
Kraft
M
M
Frank
R
R
Ansorge
S
S
D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D015696:Gene Products, tat / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D011480:Protease Inhibitors / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D015696:Gene Products, tat; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; D011480:Protease Inhibitors; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D004247:DNA; D018819:Dipeptidyl Peptidase 4