CoChat
Sign Up
Cited by 959NF-κB Signaling PathwaysGenomics and Chromatin DynamicsCytokine Signaling Pathways and Interactions

Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8.

Open access
Matsusaka, T, Fujikawa, K, Nishio, Y, Mukaida, N, Matsushima, K, Kishimoto, T, Akira, S·1993·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.90.21.10193PMC PMC47740
Open this paper in CoChat — free account

Abstract

Single binding sites for transcription factors NF-IL6 and NF-kappa B are present in the promoter of the interleukin (IL) 6 gene. Previous studies of internally deleted promoter mutants demonstrated that these two sites are important for the transcriptional regulation of this gene. In this report, we describe the synergistic activation of the IL-6 promoter by transcription factors NF-IL6 and NF-kappa B. Cotransfection of NF-IL6 with the NF-kappa B p65 subunit resulted in strong synergistic activation of an IL-6 promoter-reporter construct. Both the NF-IL6 and NF-kappa B binding sites in the IL-6 promoter were required for synergistic activation. Similar synergistic activation was observed in the IL-8 promoter, which also contains both NF-IL6 and NF-kappa B binding sites. Furthermore, we demonstrated that NF-IL6 and the NF-kappa B p65 subunit directly associated via the basic leucine-zipper domain of NF-IL6 and the Rel homology domain of p65. Since the promoters of many other genes involved in the inflammatory and acute-phase responses also contain binding sites for NF-IL6 and NF-kappa B, the cooperation between these two factors may have an important role in these responses. We also discuss the possible interplay between various viral gene products and these two factors in the process of viral infection and constitutive cytokine production.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.90.21.10193

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • IL-6 induction by LPS in hepatocytes is either occurring downstream of an alternative NFκB pathway or occurs via a completely separate mechanism.

    “This suggests that IL-6 induction by LPS is either occurring downstream of an alternative NFκB pathway or occurs via a completely separate mechanism [28], [29].”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [28]

    The Results report that LPS induces NF-κB p50 and p65 binding at the IL-6 promoter in U937 monocyte cells. That supports an LPS–NF-κB–IL-6 connection, but the paper does not establish either an alternative NF-κB pathway or a separate mechanism for IL-6 induction in hepatocytes. The cited sentence presents those possibilities as the citing authors’ inference. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • NF-κB activates the expression of cytokines such as IL6 and IL8.

    “NF-κB is also reported to activate the expression of cytokines such as IL6 and IL8 [80] (Figure 8).”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [80]

  • IL-6 transcription partially relies on NF-κB.

    “This result indicates that IL-6 transcription partially relies on NF-κB (22).”

    From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [22]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. [17]Kinoshita, S., Akira, S. & Kishimoto, T. (1992) Proc. Natl. Acad. Sci. USA 89, 1473–1476.
  2. [19]LeClair, K. P., Blanar, M. A. & Sharp, P. A. (1992) Proc. Natl. Acad. Sci. USA 89, 8145–8149.

Cited by

Sorted by citations

Authors
Matsusaka, T., Fujikawa, K., Nishio, Y., Mukaida, N., Matsushima, K., Kishimoto, T., & Akira, S.
Affiliations
The University of Osaka (JP)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1993-11
Volume
90
Issue
21
Pages
10193-10197
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.90.21.10193
PMC
PMC47740
OpenAlex
W2089478514
Cited by
959
References
2
Citations by year
2026: 12 · 2025: 11 · 2024: 9 · 2023: 15 · 2022: 11 · 2021: 23 · 2020: 11 · 2019: 20 · 2018: 19 · 2017: 25 · 2016: 23 · 2015: 29 · 2014: 22 · 2013: 25 · 2012: 25
FWCI
17.71
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
NF-IL6, NF-κB, interleukin-6, interleukin-8, transcriptional activation, promoter binding sites, p65 subunit, Rel homology domain, protein-protein interaction, inflammatory cytokines, acute phase response, viral gene products
MeSH terms
Base Sequence, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Humans, Kinetics, Molecular Sequence Data, Nuclear Proteins, Recombinant Proteins, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Interleukin-6, Gene Expression, Polymerase Chain Reaction, Interleukin-8, NF-kappa B, DNA Primers, CCAAT-Enhancer-Binding Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review