ArticlePLoS pathogens2020
Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Roles of TIR domain-containing adaptor protein in tumor: Inflammation and immune regulation via toll-like receptor signaling.The Journal of international medical research · 2026Review
- Macrophage Extracellular Traps in the Oral Mucosa: Autoimmune Disease and Platelet-Derived Epithelial Modulation.Life (Basel, Switzerland) · 2026Article
- Validating Natural Compounds as Toll-Like Receptor 4 (TLR4) Antagonists: Experimental Challenges and Therapeutic Perspectives.Journal of medicinal chemistry · 2026Review
- IFI16/IFI202 blockade suppresses tumor growth through CD8Breast cancer research : BCR · 2026Article
- METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells.Cancer medicine · 2025Article
- Involvement of Microglia in Retinal Ganglion Cell Injury Induced by IOP Elevation in a Rat Ex Vivo Acute Glaucoma Model.Biomedicines · 2025Article
- Intestinal alkaline phosphatase is a receptor for cholesterol-lowering pentapeptide IIAEK and regulates cholesterol homeostasis in mice.Scientific reports · 2025Article
- Article
- Computational Identification and Anti-Inflammatory Evaluation of T19093 as a TLR4/MD2 Inhibitor.Current topics in medicinal chemistry · 2025Article
- The role of IFI16 in regulating PANoptosis and implication in heart diseases.Cell death discovery · 2024Review
- Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.EMBO molecular medicine · 2024Review
- Human cytomegalovirus infection triggers a paracrine senescence loop in renal epithelial cells.Communications biology · 2024Article
- The Role of Oxytocin in Early-Life-Stress-Related Neuropsychiatric Disorders.International journal of molecular sciences · 2023Review
- Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth.International journal of molecular sciences · 2023Review
- Glaucoma and microglia-induced neuroinflammation.Frontiers in ophthalmology · 2023Review
- Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action.Inflammopharmacology · 2022Review
- Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin.PLoS pathogens · 2022Article
- Lupeol protects against cardiac hypertrophy via TLR4-PI3K-Akt-NF-κB pathways.Acta pharmacologica Sinica · 2022Article
- The DNA sensors AIM2 and IFI16 are SLE autoantigens that bind neutrophil extracellular traps.eLife · 2022Article
- Post-treatment with propofol inhibits inflammatory response in LPS-induced alveolar type II epithelial cells.Experimental and therapeutic medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Damage-associated molecular patterns (DAMPs) are endogenous molecules activating the immune system upon release from injured cells. Here we show that the IFI16 protein, once freely released in the extracellular milieu of chronically inflamed tissues, can function as a DAMP either alone or upon binding to lipopolysaccharide (LPS). Specifically, using pull-down and saturation binding experiments, we show that IFI16 binds with high affinity to the lipid A moiety of LPS. Remarkably, IFI16 DAMP activity is potentiated upon binding to subtoxic concentrations of strong TLR4-activating LPS variants, as judged by TLR4-MD2/TIRAP/MyD88-dependent IL-6, IL-8 and TNF-α transcriptional activation and release in stimulated monocytes and renal cells. Consistently, using co-immunoprecipitation (co-IP) and surface plasmon resonance (SPR) approaches, we show that IFI16 is a specific TLR4-ligand and that IFI16/LPS complexes display a faster stimulation turnover on TLR4 than LPS alone. Altogether, our findings point to a novel pathomechanism of inflammation involving the formation of multiple complexes between extracellular IFI16 and subtoxic doses of LPS variants, which then signal through TLR4.
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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.