TY - JOUR
T1 - Involvement of a NF-κB-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines
AU - Shimizu, Hiroko
AU - Mitomo, Katsuyuki
AU - Watanabe, Tomoo
AU - Okamoto, Shuichi
AU - Yamamoto, Ken Ichi
PY - 1990/2
Y1 - 1990/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0025138248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025138248&partnerID=8YFLogxK
U2 - 10.1128/MCB.10.2.561
DO - 10.1128/MCB.10.2.561
M3 - Article
C2 - 2405250
AN - SCOPUS:0025138248
VL - 10
SP - 561
EP - 568
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 2
ER -