title: Regulation of TNF-alpha and IL-1 gene expression during TPA-induced differentiation of "Malignant histiocytosis" DEL cell line t(5;6) (q35:p21).
abstract: The production of TNF-alpha and IL-1 alpha and beta molecules has been shown to be associated with the proliferation and activation of cells of the monocyte/macrophage series, the intermediate steps in the synthesis of these molecules have been less investigated. Unstimulated and TPA stimulated DEL cells (a CD30-positive, t(5;6)(q35;p21) malignant histiocytosis cell line) were used to study the expression of TNF-alpha and IL-1 genes and to evaluate, by nuclear run-on assay and biological measurements, the control of their transcription and the level of protein production. To refine this analysis, the effects of cycloheximide and actinomycin D were also evaluated in this investigation. Following TPA stimulation, transcription of TNF-alpha (constitutively present) increased threefold as early as 30 mins and started decreasing by 24h. Cycloheximide superinduced the expression of TNF-alpha mRNA and, accordingly, the release of its protein. By contrast, transcription of IL-1 molecules appeared de novo and did not result in a biologically detectable protein. Measurements of RNA half line after actinomycin D indicated that TNF-a and IL-1 alpha mRNAs are not as stable as that of IL-1 beta. These results indicate that, despite their common synergistic activity, the transcriptional and post-transcriptional mechanisms regulating the synthesis of TNF-alpha and IL-1 alpha and IL-1 beta involve different pathways.
authors.affiliation: I.N.S.E.R.M U 90, Hôpital Necker, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Gogusev
authors.forename: S
authors.initials: S
authors.lastname: Barbey
authors.forename: C
authors.initials: C
authors.lastname: Nezelof
mesh_terms: D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D054747:Histiocytic Sarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate