ArticleBiochimica et biophysica acta2016
Syk negatively regulates TLR4-mediated IFNβ and IL-10 production and promotes inflammatory responses in dendritic cells.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Isoimperatorin alleviates fungal keratitis by regulating NF-κB pathway and macrophage immune response.Frontiers in immunology · 2026Article
- Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling.Frontiers in immunology · 2025Article
- Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle.Frontiers in molecular neuroscience · 2024Article
- Establishment of a mandible defect model in rabbits infected with multiple bacteria and bioinformatics analysis.Frontiers in bioengineering and biotechnology · 2024Article
- Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection.Open life sciences · 2023Article
- A Novel TLR4-SYK Interaction Axis Plays an Essential Role in the Innate Immunity Response in Bovine Mammary Epithelial Cells.Biomedicines · 2022Article
- Comparison of the Chemical Components, Efficacy and Mechanisms of Action ofInternational journal of molecular sciences · 2022Article
- Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage.Frontiers in immunology · 2022Article
- Systems biology approach highlights mechanistic differences between Crohn's disease and ulcerative colitis.Scientific reports · 2021Article
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites.Frontiers in immunology · 2021Review
- Syk-MyD88 Axis Is a Critical Determinant of Inflammatory-Response in Activated Macrophages.Frontiers in immunology · 2021Article
- CD73 alleviates GSDMD-mediated microglia pyroptosis in spinal cord injury through PI3K/AKT/Foxo1 signaling.Clinical and translational medicine · 2021Article
- TLR4 induced Wnt3a-Dvl3 restrains the intensity of inflammation and protects against endotoxin-driven organ failure through GSK3β/β-catenin signaling.Molecular immunology · 2020Article
- Review
- The Mycobacterial Adjuvant Analogue TDB Attenuates Neuroinflammation via Mincle-Independent PLC-γ1/PKC/ERK Signaling and Microglial Polarization.Molecular neurobiology · 2019Article
- Regulatory Dendritic Cells Induced by K313 Display Anti-Inflammatory Properties and Ameliorate Experimental Autoimmune Encephalitis in Mice.Frontiers in pharmacology · 2019Article
- Screening of Antiviral Components of Ma Huang Tang and Investigation on the Ephedra Alkaloids Efficacy on Influenza Virus Type A.Frontiers in pharmacology · 2019Article
- Three Novel Players: PTK2B, SYK, and TNFRSF21 Were Identified to Be Involved in the Regulation of Bovine Mastitis Susceptibility via GWAS and Post-transcriptional Analysis.Frontiers in immunology · 2019Article
- Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia.Neural plasticity · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundWhile Syk has been shown to associate with TLR4, the immune consequences of Syk-TLR interactions and related molecular mechanisms are unclear.
methodsGain- and loss-of-function approaches were utilized to determine the regulatory function of Syk and elucidate the related molecular mechanisms in TLR4-mediated inflammatory responses. Cytokine production was measured by ELISA and phosphorylation of signaling molecules determined by Western blotting.
resultsSyk deficiency in murine dendritic cells resulted in the enhancement of LPS-induced IFNβ and IL-10 but suppression of pro-inflammatory cytokines (TNFα, IL-6). Deficiency of Syk enhanced the activity of PI3K and elevated the phosphorylation of PI3K and Akt, which in turn, lead to the phospho-inactivation of the downstream, central gatekeeper of the innate response, GSK3β. Inhibition of PI3K or Akt abrogated the ability of Syk deficiency to enhance IFNβ and IL-10 in Syk deficient cells, confirmed by the overexpression of Akt (Myr-Akt) or constitutively active GSK3β (GSK3 S9A). Moreover, neither inhibition of PI3K-Akt signaling nor neutralization of de novo synthesized IFNβ could rescue TNFα and IL-6 production in LPS-stimulated Syk deficient cells. Syk deficiency resulted in decreased phosphorylation of IKKβ and the NF-κB p65 subunit, further suggesting a divergent influence of Syk on pro- and anti-inflammatory TLR responses.
conclusionsSyk negatively regulates TLR4-mediated production of IFNβ and IL-10 and promotes inflammatory responses in dendritic cells through divergent regulation of downstream PI3K-Akt and NF-κB signaling pathways. GENERAL SIGNIFICANCE: Syk may represent a novel target for manipulating the direction or intensity of the innate response, depending on clinical necessity.
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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.