title: Down-regulation of interleukin-2 receptor gene activation and protein expression by dideoxynucleoside analogs.
abstract: The in vitro effect of single or combined doses of zidovudine (AZT) and dideoxycytidine (ddC) on the production and utilization of interleukin-2 (IL-2) by normal human peripheral blood mononuclear cells (PBMC) was evaluated by measuring IL-2 concentrations in supernatants from PHA-stimulated PBMC cultures. Drugs were added at the beginning of the culture period and left throughout. Whereas AZT alone (1 and 10 microM) caused only a slight increase, ddC alone (1 and 10 microM) and combined AZT/ddC (1 + 1 and 10 + 10 microM) caused a considerable increase. IL-2 gene expression in the drug-treated PBMC did not increase. This finding suggested that the increased supernatant IL-2 accumulations might be caused by a drug-induced down-regulation of the IL-2 receptor alpha (IL-2R alpha, CD25). AZT decreased IL-2R alpha expression, but only slightly. In contrast, ddC alone and combined AZT/ddC decreased the CD25 molecules in a marked and dose-dependent manner. They also markedly reduced IL-2R alpha gene expression. These findings show that the dideoxynucleoside drugs tested left PHA-induced IL-2 gene activation unchanged but decreased IL-2R alpha gene activation, thus down-regulating IL-2R alpha cell-surface protein expression.
authors.affiliation: Department of Immunology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Viora
authors.forename: B
authors.initials: B
authors.lastname: Camponeschi
mesh_terms: D000954:Antigens, Surface; D001483:Base Sequence; D002455:Cell Division; D015224:Dideoxynucleosides / Q000494:pharmacology*; D015536:Down-Regulation / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D015533:Transcriptional Activation; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D015224:Dideoxynucleosides; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011506:Proteins; D015375:Receptors, Interleukin-2; D015215:Zidovudine; D016047:Zalcitabine