ArticleNature immunology2011
Tumor necrosis factor induces GSK3 kinase-mediated cross-tolerance to endotoxin in macrophages.
Article in Nature immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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Who cites it
104 citing papers in PubMed, 164 citations in OpenAlex.
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- Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Endotoxin tolerance, a key mechanism for suppressing excessive inflammatory cytokine production, is induced by prior exposure of macrophages to Toll-like receptor (TLR) ligands. Induction of cross-tolerance to endotoxin by endogenous cytokines has not been investigated. Here we show that prior exposure to tumor necrosis factor (TNF) induced a tolerant state in macrophages, with less cytokine production after challenge with lipopolysaccharide (LPS) and protection from LPS-induced death. TNF-induced cross-tolerization was mediated by suppression of LPS-induced signaling and chromatin remodeling. TNF-induced cross-tolerance was dependent on the kinase GSK3, which suppressed chromatin accessibility and promoted rapid termination of signaling via the transcription factor NF-κB by augmenting negative feedback by the signaling inhibitors A20 and IκBα. Our results demonstrate an unexpected homeostatic function for TNF and a GSK3-mediated mechanism for the prevention of prolonged and excessive inflammation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.