title: Superinduction of IL-2 gene transcription in the presence of cycloheximide.
abstract: Lymphokine production is regulated both at the transcriptional and the posttranscriptional level. To date, it has been shown that the protein synthesis inhibitor cycloheximide (CHX) up-regulates IL-2 expression in T cells by stabilizing its mRNA. In this report we have examined the effect of CHX on IL-2 at the transcriptional level. We have found that CHX has a positive regulatory function in IL-2 transcription, which is dependent on prior activation of this gene. This is not due to posttranslational conversion of inactive NFkB into its active form by CHX, because a clustered mutation in the kB-like sequence in the IL-2 enhancer that abrogates NFkB binding does not affect the up-regulation of IL-2 transcription. These results favor the hypothesis that, in addition to positive factors, negative elements regulate IL-2 transcription. Furthermore, we have tested the effect of CHX on IL-4 and granulocyte-macrophage-CSF transcription of both lymphokines. These results suggest that transcriptional up-regulation by CHX may be specific for IL-2 with respect to lymphokine expression.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: A M
authors.initials: AM
authors.lastname: Zubiaga
authors.forename: E
authors.initials: E
authors.lastname: Muñoz
authors.forename: B T
authors.initials: BT
authors.lastname: Huber
mesh_terms: D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000032:analysis; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D007376:Interleukin-2; D012333:RNA, Messenger; D015847:Interleukin-4; D015759:Ionomycin; D003513:Cycloheximide; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate