Downregulation of interleukin 8 gene expression in human fibroblasts: Unique mechanism of transcriptional inhibition by interferon

Igor C. Oliveira, Peter J. Sciavolino, Tae H. Lee, Jan Vilček

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

The chemotactic cytokine interleukin 8 (IL-8) is produced upon stimulation by various agents in many cell types, including connective-tissue fibroblasts. Tumor necrosis factor (TNF) and IL-1 are potent inducers of IL-8 expression. Earlier we showed that TNF-induced stimulation of IL-8 mRNA accumulation in human FS-4 fibroblasts was inhibited by interferon β (IFN-β) or IFN-γ. Here we show that this inhibition is not specific for TNF, since IFN-β also reduced IL-8 mRNA accumulation induced by IL-1 or the double-stranded RNA poly (I·C). Treatment with IFN-γ also decreased TNF-induced IL-8 protein accumulation. Interestingly, the inhibitory effect was much less pronounced when IFN-β was added ≥1 hr before TNF. The inhibitory action of IFN-β on IL-8 mRNA accumulation was undiminished in the presence of inhibitors of protein synthesis. Nuclear run-on assays demonstrated that IFN-β caused a marked inhibition of TNF-induced IL-8 gene transcription; the transcriptional activation of several other TNF-induced genes was not inhibited by IFN-β. The results suggest that the specific inhibition of the transcriptional activation of IL-8 by IFN is due either to a transient inactivation of a factor required for IL-8 transcription or to the activation of a selective inhibitory factor.

Original languageEnglish
Pages (from-to)9049-9053
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number19
DOIs
Publication statusPublished - 1992 Oct 1

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Interleukin-8
Interferons
Down-Regulation
Fibroblasts
Gene Expression
Tumor Necrosis Factor-alpha
Interleukin-1
Messenger RNA
Transcriptional Activation
Connective Tissue Cells
Protein Synthesis Inhibitors
Double-Stranded RNA
Chemokines
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "The chemotactic cytokine interleukin 8 (IL-8) is produced upon stimulation by various agents in many cell types, including connective-tissue fibroblasts. Tumor necrosis factor (TNF) and IL-1 are potent inducers of IL-8 expression. Earlier we showed that TNF-induced stimulation of IL-8 mRNA accumulation in human FS-4 fibroblasts was inhibited by interferon β (IFN-β) or IFN-γ. Here we show that this inhibition is not specific for TNF, since IFN-β also reduced IL-8 mRNA accumulation induced by IL-1 or the double-stranded RNA poly (I·C). Treatment with IFN-γ also decreased TNF-induced IL-8 protein accumulation. Interestingly, the inhibitory effect was much less pronounced when IFN-β was added ≥1 hr before TNF. The inhibitory action of IFN-β on IL-8 mRNA accumulation was undiminished in the presence of inhibitors of protein synthesis. Nuclear run-on assays demonstrated that IFN-β caused a marked inhibition of TNF-induced IL-8 gene transcription; the transcriptional activation of several other TNF-induced genes was not inhibited by IFN-β. The results suggest that the specific inhibition of the transcriptional activation of IL-8 by IFN is due either to a transient inactivation of a factor required for IL-8 transcription or to the activation of a selective inhibitory factor.",
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Downregulation of interleukin 8 gene expression in human fibroblasts : Unique mechanism of transcriptional inhibition by interferon. / Oliveira, Igor C.; Sciavolino, Peter J.; Lee, Tae H.; Vilček, Jan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 19, 01.10.1992, p. 9049-9053.

Research output: Contribution to journalArticle

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