ArticleBiomolecules2020
Tryptophanyl-tRNA Synthetase 1 Signals Activate TREM-1 via TLR2 and TLR4.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Integrative Proteogenomics and Single-Cell Transcriptomics Prioritize Candidate Causal Proteins and Therapeutic Targets in Age-Related Macular Degeneration.International journal of molecular sciences · 2026Article
- Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study.Eye (London, England) · 2026Article
- Beyond Hemostasis: Platelet Biomarkers and Vascular-Immune Crosstalk in Dengue.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Troxerutin suppresses the stemness of hepatocellular carcinoma via the Syk/FOXO3 feedback loop.Cell biology and toxicology · 2026Article
- Dietary silver nanoparticle supplementation induces Alzheimer-like lesions through Bifidobacterium deficiency-dominated gut microbiota dysbiosis and neuroinflammation.NPJ science of food · 2026Article
- HIV gp120 induces TREM1 expression through TLR-PGE₂ signalling in human monocyte-derived microglia.Journal of neuroinflammation · 2026Article
- Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities.Frontiers in immunology · 2026Review
- Proteomic and functional analysis on endothelial cell heterogeneity identifies key regulators in hyperglycemia-induced dysfunction.American journal of physiology. Cell physiology · 2025Article
- Progressively altered genes in colorectal carcinogenesis link oncogenesis immune cycle and tumor microenvironment.Scientific reports · 2025Article
- Single-cell and bulk transcriptome analysis unveils a ligand-receptor-based signature for prognostication and reveals that TREM1 controls the malignant behaviors of hepatocellular carcinoma.Acta biochimica et biophysica Sinica · 2025Article
- Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population.Translational vision science & technology · 2025Article
- Integrating plasma proteomics and genome-wide association data to identify therapeutic targets for retinal neurodegenerative diseases in Europeans.International journal of ophthalmology · 2025Article
- Human pulmonary microvascular endothelial cells respond to DAMPs from injured renal tubular cells.Pulmonary circulation · 2024Article
- Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.International journal of molecular sciences · 2024Review
- Dysregulation of CD4Journal for immunotherapy of cancer · 2024Article
- Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model.The journal of headache and pain · 2024Article
- Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis.EMBO molecular medicine · 2024Article
- Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2023Review
- Identification of Potentially Novel Molecular Targets of Endometrial Cancer Using a Non-Biased Proteomic Approach.Cancers · 2023Article
- Potential disease biomarkers for diabetic retinopathy identified through Mendelian randomization analysis.Frontiers in endocrinology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tryptophanyl-tRNA synthetase 1 (WARS1) is an endogenous ligand of mammalian Toll-like receptors (TLR) 2 and TLR4. Microarray data, using mRNA from WARS1-treated human peripheral blood mononuclear cells (PBMCs), had indicated WARS1 to mainly activate innate inflammatory responses. However, exact molecular mechanism remains to be understood. The triggering receptor expressed on myeloid cells (TREM)-1 is an amplifier of pro-inflammatory processes. We found WARS1 to significantly activate TREM-1 at both mRNA and protein levels, along with its cell surface expression and secretion in macrophages. WARS1 stimulated TREM-1 production via TLR2 and TLR4, mediated by both MyD88 and TRIF, since targeted deletion of TLR4, TLR2, MyD88, and TRIF mostly abrogated TREM-1 activation. Furthermore, WARS1 promoted TREM-1 downstream phosphorylation of DAP12, Syk, and AKT. Knockdown of TREM-1 and inhibition of Syk kinase significantly suppressed the activation of inflammatory signaling loop from MyD88 and TRIF, leading to p38 MAPK, ERK, and NF-κB inactivation. Finally, MyD88, TRIF, and TREM-1 signaling pathways were shown to be cooperatively involved in WARS1-triggered massive production of IL-6, TNF-α, IFN-β, MIP-1α, MCP-1, and CXCL2, where activation of Syk kinase was crucial. Taken together, our data provided a new insight into WARS1's strategy to amplify innate inflammatory responses via TREM-1.
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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.