Immunity 2006,
PMID: 16413922
Kuwata, Hirotaka; Matsumoto, Makoto; Atarashi, Koji; Morishita, Hideaki; Hirotani, Tomohiro; Koga, Ritsuko; Takeda, Kiyoshi
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 IkappaBNS, a TLR-inducible nuclear IkappaB protein, negatively regulates induction of a subset of TLR-dependent genes through inhibition of NF-kappaB activity. IkappaBNS-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, IkappaBNS-deficient cells showed normal induction of genes that are induced early or induced via IRF-3 activation. LPS stimulation of IkappaBNS-deficient macrophages prolonged NF-kappaB activity at the specific promoters, indicating that IkappaBNS mediates termination of NF-kappaB activity at selective gene promoters. Moreover, IkappaBNS-deficient mice are highly susceptible to LPS-induced endotoxin shock and intestinal inflammation. Thus, IkappaBNS regulates inflammatory responses by inhibiting the induction of a subset of TLR-dependent genes through modulation of NF-kappaB activity.
Diseases/Pathways annotated by Medline MESH: Colitis, Shock, Septic
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Text Mining Data
IL-12p40 → TLR: "
IkappaBNS-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
"
IL-12p40 → TLR: "
IkappaBNS-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
"
IL-6 → TLR: "
IkappaBNS-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
"
Manually curated Databases
No curated data.