IκBNS inhibits induction of a subset of toll-like receptor-dependent genes and limits inflammation

Hirotaka Kuwata, Makoto Matsumoto, Koji Atarashi, Hideaki Morishita, Tomohiro Hirotani, Ritsuko Koga, Kiyoshi Takeda

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Toll-like receptor (TLR)-mediated immune responses are downregulated by several mechanisms that affect signaling pathways. However, it remains elusive how TLR-mediated gene expression is differentially modulated. Here, we show that IκBNS, a TLR-inducible nuclear IκB protein, negatively regulates induction of a subset of TLR-dependent genes through inhibition of NF-κB activity. IκBNS-deficient macrophages and dendritic cells show increased TLR-mediated expression of genes such as IL-6 and IL-12p40, which are induced late after TLR stimulation. In contrast, IκBNS-deficient cells showed normal induction of genes that are induced early or induced via IRF-3 activation. LPS stimulation of IκBNS-deficient macrophages prolonged NF-κB activity at the specific promoters, indicating that IκBNS mediates termination of NF-κB activity at selective gene promoters. Moreover, IκBNS-deficient mice are highly susceptible to LPS-induced endotoxin shock and intestinal inflammation. Thus, IκBNS regulates inflammatory responses by inhibiting the induction of a subset of TLR-dependent genes through modulation of NF-κB activity.

Original languageEnglish
Pages (from-to)41-51
Number of pages11
JournalImmunity
Volume24
Issue number1
DOIs
Publication statusPublished - 2006 Jan
Externally publishedYes

Fingerprint

Toll-Like Receptors
Inflammation
Genes
Macrophages
Interleukin-12 Subunit p40
Gene Expression
Nuclear Proteins
Endotoxins
Dendritic Cells
Shock
Interleukin-6
Down-Regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

IκBNS inhibits induction of a subset of toll-like receptor-dependent genes and limits inflammation. / Kuwata, Hirotaka; Matsumoto, Makoto; Atarashi, Koji; Morishita, Hideaki; Hirotani, Tomohiro; Koga, Ritsuko; Takeda, Kiyoshi.

In: Immunity, Vol. 24, No. 1, 01.2006, p. 41-51.

Research output: Contribution to journalArticle

Kuwata, H, Matsumoto, M, Atarashi, K, Morishita, H, Hirotani, T, Koga, R & Takeda, K 2006, 'IκBNS inhibits induction of a subset of toll-like receptor-dependent genes and limits inflammation', Immunity, vol. 24, no. 1, pp. 41-51. https://doi.org/10.1016/j.immuni.2005.11.004
Kuwata, Hirotaka ; Matsumoto, Makoto ; Atarashi, Koji ; Morishita, Hideaki ; Hirotani, Tomohiro ; Koga, Ritsuko ; Takeda, Kiyoshi. / IκBNS inhibits induction of a subset of toll-like receptor-dependent genes and limits inflammation. In: Immunity. 2006 ; Vol. 24, No. 1. pp. 41-51.
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