ArticleJournal of leukocyte biology2011
Induction of endotoxin tolerance in vivo inhibits activation of IRAK4 and increases negative regulators IRAK-M, SHIP-1, and A20.
Article in Journal of leukocyte biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Pooled it
- Pooled it
- Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19.Journal of leukocyte biology · 2021Trial
- Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series.BMC infectious diseases · 2014Trial
- Mitochondrial DAMPs induce endotoxin tolerance in human monocytes: an observation in patients with myocardial infarction.PloS one · 2014Trial
- Dissection of MAPK and NF-κB p65 signaling dynamics underlying LPS tolerance in macrophages at the single-cell level.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Optimising the induction of inflammation within preterm infant-derived intestinal epithelial organoids.Npj gut and liver · 2026Article
- Inflammatory disease status and response to TNF blockade are associated with mechanisms of endotoxin tolerance.Journal of autoimmunity · 2024Article
- Endotoxin tolerance and trained immunity: breaking down immunological memory barriers.Frontiers in immunology · 2024Review
- Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet.Frontiers in nutrition · 2024Article
- Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics.Pharmaceutics · 2023Review
- Training vs. Tolerance: The Yin/Yang of the Innate Immune System.Biomedicines · 2023Review
- Screening of compounds to identify novel epigenetic regulatory factors that affect innate immune memory in macrophages.Scientific reports · 2022Article
- Role of Specialized Pro-Resolving Mediators in Modifying Host Defense and Decreasing Bacterial Virulence.Molecules (Basel, Switzerland) · 2021Review
- Lipopolysaccharide-Induced Exosomal miR-146a Is Involved in Altered Expression of Alzheimer's Risk Genes Via Suppression of TLR4 Signaling.Journal of molecular neuroscience : MN · 2021Article
- Manifestation of lipopolysaccharide-induced tolerance in neuro-glial primary cultures of the rat afferent somatosensory system.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
- Reversing Post-Infectious Epigenetic-Mediated Immune Suppression.Frontiers in immunology · 2021Review
- The Modulatory Activity of Tryptophan Displaying Nanodevices on Macrophage Activation for Preventing Acute Lung Injury.Frontiers in immunology · 2021Article
- Targeting Neutrophils in Sepsis: From Mechanism to Translation.Frontiers in pharmacology · 2021Review
- The soluble tumor necrosis factor receptor 1 as a potential early diagnostic and prognostic markers in intensive care unit patients with severe infections.Central-European journal of immunology · 2020Article
5 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
2 authors at 1 institution in 1 country.
Funding
Abstract
TLRs mediate host defense against microbial pathogens by eliciting production of inflammatory mediators and activating expression of MHC, adhesion, and costimulatory molecules. Endotoxin tolerance limits excessive TLR-driven inflammation during sepsis and reprograms macrophage responses to LPS, decreasing expression of proinflammatory cytokines without inhibiting anti-inflammatory and antimicrobial mediators. Molecular mechanisms of reprogramming of TLR4 signaling upon in vivo induction of endotoxin tolerance are incompletely understood. We used an in vivo model of endotoxin tolerance, whereby C57BL/6 mice were i.p.-inoculated with LPS or PBS, followed by in vitro challenge of peritoneal or splenic macrophages with LPS to examine activation of IRAK4 and expression of negative regulatory molecules. Administration of LPS in vivo-induced endotoxin tolerance in peritoneal and splenic macrophages, as evidenced by decreased degradation of IκBα, suppressed phosphorylation of p38 and reduced expression of TNF-α, IL-6, and KC mRNA upon in vitro LPS challenge. Macrophages from control and endotoxin-tolerant mice exhibited comparable TLR4 mRNA levels and similar expression of IL-1RA and IL-10 genes. Endotoxin tolerization in vivo blocked TLR4-driven IRAK4 phosphorylation and activation in macrophages, while increasing expression of IRAK-M, SHIP-1, A20 mRNA, and A20 protein. Thus, induction of endotoxin tolerance in vivo inhibits expression of proinflammatory mediators via impaired activation of IRAK4, p38, and NF-κB and increases expression of negative regulators of TLR4 pathways.
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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.