ArticleMolecular immunology2020
TLR4 induced Wnt3a-Dvl3 restrains the intensity of inflammation and protects against endotoxin-driven organ failure through GSK3β/β-catenin signaling.
Article in Molecular immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
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- A novel peptide-compound conjugate alleviates endotoxin-induced inflammation via NF-κB/MAPK modulation.Journal of molecular medicine (Berlin, Germany) · 2025Article
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- A Protective Role of Canonical Wnt/Mediators of inflammation · 2024Review
- Circular RNA circSMAD4 regulates cardiac fibrosis by targeting miR-671-5p andMolecular therapy. Nucleic acids · 2023Article
- Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells.Microbiology spectrum · 2023Article
- SGK1 negatively regulates inflammatory immune responses and protects against alveolar bone loss through modulation of TRAF3 activity.The Journal of biological chemistry · 2022Article
- Article
- The 'Danse Macabre'-Neutrophils the Interactive Partner Affecting Oral Cancer Outcomes.Frontiers in immunology · 2022Review
- MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway.Experimental and therapeutic medicine · 2021Article
- Genome-Wide Gene Expression Analysis of Mtb-Infected DC Highlights the Rapamycin-Driven Modulation of Regulatory CytokinesFrontiers in immunology · 2021Article
- Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites.Frontiers in immunology · 2021Review
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- Wnt Pathway: An Integral Hub for Developmental and Oncogenic Signaling Networks.International journal of molecular sciences · 2020Review
- JAK3 restrains inflammatory responses and protects against periodontal disease through Wnt3a signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAccumulating evidence suggests a regulatory role of Wnt proteins in innate immune responses. However, the effects of Wnt3a signaling on TLR4-mediated inflammatory responses are controversial and the signaling crosstalk between TLR4 and Wnt3a remains uncertain.
methodsGain- and Loss- of function approaches were utilized to determine the function of Wnt3a signaling in TLR4-mediated inflammatory responses. Cytokine production at protein and mRNA levels and phosphorylation of signaling molecules were measured by ELISA, qRT-PCR, and Western Blot, respectively. Endotoxemia mouse model was employed to assess the effect of Wnt3a on systemic inflammatory cytokine levels and neutrophil infiltration.
resultsLPS stimulation leads to an increase of Wnt3a expression and its downstream molecule, Dvl3, in primary monocytes. Inhibition or silence of Wnt3a or Dvl3 significantly increases the production of pro-inflammatory cytokines (IL-12, IL-6, TNFα), robustly reduces β-catenin accumulation, and enhances the phosphorylation of NF-κB P65 and its DNA binding activity. These results were confirmed by multiple gain- and loss- of function approaches including specific siRNA and ectopic expression of Dvl3, GSK3β, and β-catenin in monocytes. Moreover, in vivo relevance was established in a murine endotoxin model, in which Wnt3a inhibition enhances the inflammatory responses by augmenting the systemic pro-inflammatory cytokine levels and neutrophil infiltration.
conclusionsTLR4 activation promotes Wnt3a-Dvl3 signaling, which acts as rheostats to restrain the intensity of inflammation through regulating GSK3β-β-catenin signaling and NF-κB activity. GENERAL SIGNIFICANCE: Wnt3a-Dvl3-β-catenin signaling axis could be a potential interventional target for manipulating the direction and intensity of inflammatory responses.
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