ReviewBritish journal of pharmacology2012
The SYK side of TLR4: signalling mechanisms in response to LPS and minimally oxidized LDL.
Review in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 165 citations in OpenAlex.
- TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.Mediators of inflammation · 2014Trial
- Toll-like receptor 4 signaling links cytoskeletal remodeling to lipid accumulation in macrophages.Inflammation and regeneration · 2026Review
- Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.ImmunoHorizons · 2026Article
- A Novel Tyrosine Kinase Axis in Innate Immune Signaling.Viruses · 2025Review
- Mechanism of Neutrophil p90RSK-Nrf2 Signaling Pathway in Atherosclerosis.Balkan medical journal · 2025Article
- Syk inhibitor attenuates lupus in FcγRIIbCell death discovery · 2025Article
- Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling.Frontiers in immunology · 2025Article
- Resveratrol suppresses OSCC invasion and migration by regulating macrophage polarization via Syk signaling pathway.Frontiers in immunology · 2025Article
- Regulation of lipid storage and inflammation in the liver by CEACAM1.European journal of clinical investigation · 2024Review
- Exploring the Anti-Inflammatory Effect of Tryptanthrin by Regulating TLR4/MyD88/ROS/NF-κB, JAK/STAT3, and Keap1/Nrf2 Signaling Pathways.ACS omega · 2024Article
- Transient receptor potential vanilloid 1 interacts with Toll-like receptor 4 (TLR4)/cluster of differentiation 14 (CD14) signaling pathway in lipopolysaccharide-mediated inflammation in macrophages.Experimental animals · 2024Article
- Oxyresveratrol Improves Cognitive Impairments and Episodic-like Memory through Modulating Neuroinflammation and PI3K-Akt Signaling Pathway in LPS-Induced Mice.Molecules (Basel, Switzerland) · 2024Article
- Functional Involvement of TANK-Binding Kinase 1 in the MyD88-Dependent NF-Mediators of inflammation · 2024Article
- Fostamatinib, a Spleen Tyrosine Kinase Inhibitor, Exerts Anti-Inflammatory Activity via Inhibiting STAT1/3 Signaling Pathways.Journal of inflammation research · 2024Article
- Spleen tyrosine kinase: a novel pharmacological target for sepsis-induced cardiac dysfunction and multi-organ failure.Frontiers in immunology · 2024Article
- Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway.Lipids in health and disease · 2023Article
- Thyroid-stimulating hormone may participate in insulin resistance by activating toll-like receptor 4 in liver tissues of subclinical hypothyroid rats.Molecular biology reports · 2023Article
- Article
- Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen.Nature communications · 2023Article
22 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
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Spleen tyrosine kinase (SYK) is the best known for its involvement in immune receptor signalling, mediated by binding of SYK tandem Src-homology 2 domains to tandem phosphotyrosine in immunoreceptor tyrosine-based activation motifs (ITAMs). ITAM adaptors or ITAM-containing receptor tails mediate signalling from B- and T-cell receptors, Fc receptors and many C-type lectins, including dectin-1. Recent data point to constitutive binding of SYK to the cytoplasmic domain of toll-like receptor-4 (TLR4). This SYK-TLR4 binding increases upon TLR4 dimerization and phosphorylation, and SYK plays a prominent role in TLR4 signalling in response to LPS in neutrophils and monocytes. SYK also plays an important role in TLR4-mediated macrophage responses to minimally oxidized low-density lipoprotein (mmLDL), which is a form of oxidized LDL relevant to development of human atherosclerosis. Interestingly, mmLDL-induced effects in macrophages, which occur via TLR4, are predominantly MyD88 independent. This unmasks the role of the SYK branch of TLR4 signalling, which mediates modest cytokine release via activation of AP-1 transcription and robust reactive oxygen species generation and cytoskeletal rearrangements. The latter results in extensive membrane ruffling and macropinocytosis, leading to lipoprotein uptake and foam cell formation, a hallmark of atherosclerotic lesions. Because inhibitors of SYK activity, such as fostamatinib, are in advanced clinical trials for rheumatoid arthritis and other autoimmune diseases, understanding the role of SYK in signalling via TLR4 is of immediate importance. This signalling pathway seems to be particularly important in TLR4 activation by host-derived, damage-associated molecular pattern ligands, such as mmLDL, relevant to development of atherosclerosis and other chronic inflammatory diseases.
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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.