CoChat
Sign Up
Cited by 460

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ

Yamamoto, Masahiro, Yamazaki, Soh, Uematsu, Satoshi, Sato, Shintaro, Hemmi, Hiroaki, Hoshino, Katsuaki, Kaisho, Tsuneyasu, Kuwata, Hirotaka, Takeuchi, Osamu, Takeshige, Koichiro, Saitoh, Tatsuya, Yamaoka, Shoji, Yamamoto, Naoki, Yamamoto, Shunsuke, Muta, Tatsushi, Takeda, Kiyoshi, Akira, Shizuo·2004·Nature
DOI 10.1038/nature02738
Open this paper in CoChat — free account

Abstract

Toll-like receptors (TLRs) recognize microbial components and trigger the inflammatory and immune responses against pathogens. IkappaBzeta (also known as MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1 (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient cells show severe impairment of IL-6 production in response to a variety of TLR ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha. Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB, and is recruited to the NF-kappaB binding site of the IL-6 promoter on stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages. Given that the lipopolysaccharide-induced transcription of IkappaBzeta occurs earlier than transcription of these genes, some TLR/IL-1R-mediated responses may be regulated in a gene expression process of at least two steps that requires inducible IkappaBzeta.

Overview

Integrity signals

Registry

Crossref · 10.1038/nature02738

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Citations

Cites

Show all 6 references

Research works printed but not linked: 24

  1. O'Neill, L. A. Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. Curr. Opin. Pharmacol. 3, 396–403 (2003) · DOI
  2. Yamazaki, S., Muta, T. & Takeshige, K. A novel IκB protein, IκB-ζ, induced by proinflammatory stimuli, negatively regulates nuclear factor-κB in the nuclei. J. Biol. Chem. 276, 27657–27662 (2001) · DOI
  3. Kitamura, H., Kanehira, K., Okita, K., Morimatsu, M. & Saito, M. MAIL, a novel nuclear IκB protein that potentiates LPS-induced IL-6 production. FEBS Lett. 485, 53–56 (2000) · DOI
  4. Haruta, H., Kato, A. & Todokoro, K. Isolation of a novel interleukin-1-inducible nuclear protein bearing ankyrin-repeat motifs. J. Biol. Chem. 276, 12485–12488 (2001) · DOI
  5. Muzio, M., Ni, J., Feng, P. & Dixit, V. M. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278, 1612–1615 (1997) · DOI
  6. Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S. & Cao, Z. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7, 837–847 (1997) · DOI
  7. Medzhitov, R. et al. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 2, 253–258 (1998) · DOI
  8. Kawai, T. et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167, 5887–5894 (2001) · DOI
  9. Doyle, S. et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17, 251–263 (2002) · DOI
  10. Zhang, G. & Ghosh, S. Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J. Endotoxin Res. 6, 453–457 (2000) · DOI
  11. Janssens, S. & Beyaert, R. Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol. Cell 11, 293–302 (2003) · DOI
  12. Eto, A., Muta, T., Yamazaki, S. & Takeshige, K. Essential roles for NF-κB and a Toll/IL-1 receptor domain-specific signal(s) in the induction of IκB-ζ. Biochem. Biophys. Res. Commun. 301, 495–501 (2003) · DOI
  13. Akira, S., Taga, T. & Kishimoto, T. Interleukin-6 in biology and medicine. Adv. Immunol. 54, 1–78 (1993) · DOI
  14. Zhong, H., May, M. J., Jimi, E. & Ghosh, S. The phosphorylation status of nuclear NF-κB determines its association with CBP/p300 or HDAC-1. Mol. Cell 9, 625–636 (2002) · DOI
  15. Sha, W. C., Liou, H. C., Tuomanen, E. I. & Baltimore, D. Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses. Cell 80, 321–330 (1995) · DOI
  16. Sanjabi, S., Hoffmann, A., Liou, H. C., Baltimore, D. & Smale, S. T. Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages. Proc. Natl Acad. Sci. USA 97, 12705–12710 (2000) · DOI
  17. Hoffmann, A., Leung, T. H. & Baltimore, D. Genetic analysis of NF-κB/Rel transcription factors defines functional specificities. EMBO J. 22, 5530–5539 (2003) · DOI
  18. Hill, M. R. & McCallum, R. E. Identification of tumor necrosis factor as a transcriptional regulator of the phosphoenolpyruvate carboxykinase gene following endotoxin treatment of mice. Infect. Immun. 60, 4040–4050 (1992) · DOI
  19. Pasparakis, M. et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417, 861–866 (2002) · DOI
  20. Douni, E. et al. Transgenic and knockout analyses of the role of TNF in immune regulation and disease pathogenesis. J. Inflamm. 47, 27–38 (1995)
  21. Yamamoto, M. et al. Role of adaptor TRIF in the MyD88-independent Toll-Like Receptor signaling pathway. Science 301, 640–643 (2003) · DOI
  22. Saitoh, T. et al. TWEAK induces NF-κB2 p100 processing and long lasting NF-κB activation. J. Biol. Chem. 278, 36005–36012 (2003) · DOI
  23. Toshchakov, V. et al. TLR4, but not TLR2, mediates IFN-β-induced STAT1α/β-dependent gene expression in macrophages. Nature Immunol. 3, 392–398 (2002) · DOI
  24. Kuwata, H. et al. IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-α production in macrophages. Blood 102, 4123–4129 (2003) · DOI

Cited by

Metadata

Authors
Yamamoto, M., Yamazaki, S., Uematsu, S., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Kuwata, H., Takeuchi, O., Takeshige, K., Saitoh, T., Yamaoka, S., Yamamoto, N., Yamamoto, S., Muta, T., Takeda, K., & Akira, S.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2004-07
Volume
430
Issue
6996
Pages
218-222
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature02738
Cited by
460
References
6
Language
en
Licence
www.springer.com/tdm (tdm)

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