Polyamine biosynthesis is necessary for interleukin-2-dependent proliferation but not for interleukin-2 production or high-affinity interleukin-2 receptor expression.
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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D000518:Eflornithine / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology
D007376:Interleukin-2; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D004247:DNA; D011700:Putrescine; D000518:Eflornithine