Differential induction of the interleukin-6 gene by tumor necrosis factor and interleukin-1.
Although tumor necrosis factor (TNF) and interleukin-1 (IL) induce the expression of the IL-8, TNF-stimulated gene 6, and plasminogen activation inhibitor-2 genes and the activation of NF-kappa B with nearly identical kinetics, the two cytokines differ significantly in the induction of the IL-6 gene in all primary fibroblasts tested. IL-1 induces IL-6 gene expression after 30 min of IL-1 treatment, reaching a maximum level by 7 h, and is sustained for up to 14 h. TNF also induces the IL-6 gene expression at 30 min but the induction was low. A similar differences in the amount of IL-6 secreted was observed in the IL-1/TNF-treated cells. Measurement of IL-6 gene transcription by nuclear run-on transcription assays indicated a 4-fold higher rate of IL-6 gene transcription in IL-1-treated than in TNF-treated cells. The IL-1-induced IL-6 mRNA has a significantly longer half-life (> 6 h) compared to 30 min for TNF-treated cells. These results suggest that the induction of the IL-6 gene expression in primary human fibroblasts by TNF and IL-1 is differentially regulated at the transcriptional as well as at the post-transcriptional level.
Institute of Molecular and Cell Biology, National University of Singapore, Republic of Singapore.
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SB
Ng
Y H
YH
Tan
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GR
Guy
D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin