Polyamine biosynthesis is necessary for interleukin-2-dependent proliferation but not for interleukin-2 production of high-affinity interleukin-2 receptor expression

• Published in: Journal of biochemistry (Tokyo) 1987-12, Vol.102 (6), p.1469-1476
• Main Authors: YUKIOBA, K, OTANI, S, MATSUI-YUASA, I, SHIBATA, T, NISHIZAWA, Y, MORII, H, MORISAWA, S
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Concanavalin A - pharmacology; DNA - biosynthesis; Eflornithine - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunological reactions in vitro; Interleukin-2 - biosynthesis; Interleukin-2 - pharmacology; Kinetics; Lymphoblastic transformation (stimulation by antigen, mitogen, mixed lymphocyte reactions); Lymphocyte Activation - drug effects; Lymphocytes - cytology; Lymphocytes - metabolism; Male; Ornithine Decarboxylase Inhibitors; Polyamines - biosynthesis; Putrescine - pharmacology; Rats; Rats, Inbred Strains; Receptors, Immunologic - metabolism; Receptors, Interleukin-2; Spleen - cytology; T-Lymphocytes - cytology
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/oxfordjournals.jbchem.a122193

DL-alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase [EC 4.1.1.17] (ODC), inhibited concanavalin A-induced proliferation of splenic mononuclear cells (SMNC). The inhibition was not reversed by interleukin-2 (IL-2) addition. Although DFMO did not affect the production of IL-2 or the expression of high-affinity IL-2 receptor, IL-2-dependent proliferation of SMNC was inhibited by DFMO, and the inhibition was reversed by exogenous putrescine. The inhibition of IL-2-dependent DNA synthesis appeared to be related to the decrease in intracellular polyamines. When the proliferation of SMNC was induced by IL-2, ODC activity was also increased. A similar result was obtained in the proliferation of an IL-2-dependent T cell line, CTLL. The time course of ODC induction was similar to that of IL-2 production by concanavalin A-stimulated SMNC. These results indicate that polyamine biosynthesis is necessary for IL-2-dependent proliferation, but not for IL-2 production or IL-2 receptor expression.