Involvement of a NF-κB-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines

Hiroko Shimizu, Katsuyuki Mitomo, Tomoo Watanabe, Shuichi Okamoto, Ken Ichi Yamamoto

Research output: Contribution to journalArticle

304 Citations (Scopus)

Abstract

Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-α despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-κB transcription factor-binding motifs and binds an IL-1-TNF-α-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular localizations of this factor are indistinguishable from those of NF-κB. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-α in vivo. These results indicate that a nuclear factor indistinguishable from NF-κB is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-α.

Original languageEnglish
Pages (from-to)561-568
Number of pages8
JournalMolecular and Cellular Biology
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 1990
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Involvement of a NF-κB-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines'. Together they form a unique fingerprint.

  • Cite this