ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2015
The Extracellular IFI16 Protein Propagates Inflammation in Endothelial Cells Via p38 MAPK and NF-κB p65 Activation.
Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2015. 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, 33 citations in OpenAlex.
- Phytoestrogens and related microbial metabolites remodel aberrant prostate transcriptomic profiles generated upon exposure to oxidative stress.Molecular and cellular biochemistry · 2026Article
- Pre-Encoded IFN-I Sensitivity Exacerbates Memory T Cell Senescence in Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation.Communications biology · 2026Article
- IFI16/IFI202 blockade suppresses tumor growth through CD8Breast cancer research : BCR · 2026Article
- Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections.Pathogens (Basel, Switzerland) · 2025Review
- Article
- The role of IFI16 in regulating PANoptosis and implication in heart diseases.Cell death discovery · 2024Review
- Cytoplasmic DNA and AIM2 inflammasome in RA: where they come from and where they go?Frontiers in immunology · 2024Review
- Renal interferon-inducible protein 16 expression is associated with disease activity and prognosis in lupus nephritis.Arthritis research & therapy · 2023Article
- The DNA sensors AIM2 and IFI16 are SLE autoantigens that bind neutrophil extracellular traps.eLife · 2022Article
- Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding.PLoS pathogens · 2020Article
- Understanding HCMV Latency Using Unbiased Proteomic Analyses.Pathogens (Basel, Switzerland) · 2020Review
- Review
- Serum IFI16 and anti-IFI16 antibodies in psoriatic arthritis.Clinical and experimental immunology · 2020Article
- p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice.EBioMedicine · 2018Article
- The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus: The Dark Side of Sensing Microbes.Frontiers in immunology · 2018Review
- Up-regulation of Interferon-inducible protein 16 contributes to psoriasis by modulating chemokine production in keratinocytes.Scientific reports · 2016Article
- DNA Damage Response and Immune Defense: Links and Mechanisms.Frontiers in genetics · 2016Review
- Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment.BioMed research international · 2016Review
- Ligand engagement of Toll-like receptors regulates their expression in cortical microglia and astrocytes.Journal of neuroinflammation · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear interferon-inducible-16 (IFI16) protein acts as DNA sensor in inflammasome signaling and as viral restriction factor. Following Herpesvirus infection or UV-B treatment, IFI16 delocalizes from the nucleus to the cytoplasm and is eventually released into the extracellular milieu. Recently, our group has demonstrated the occurrence of IFI16 in sera of systemic-autoimmune patients that hampers biological activity of endothelia through high-affinity membrane binding. As a continuation, we studied the activity of endotoxin-free recombinant IFI16 (rIFI16) protein on primary endothelial cells. rIFI16 caused dose/time-dependent upregulation of IL-6, IL-8, CCL2, CCL5, CCL20, ICAM1, VCAM1, and TLR4, while secretion of IL-6 and IL-8 was amplified with lipopolysaccharide synergy. Overall, cytokine secretion was completely inhibited in MyD88-silenced cells and partially by TLR4-neutralizing antibodies. By screening downstream signaling pathways, we found that IFI16 activates p38, p44/42 MAP kinases, and NF-kB. In particular, activation of p38 is an early event required for subsequent p44/42 MAP kinases activity and cytokine induction indicating a key role of this kinase in IFI16 signaling. Altogether, our data conclude that extracellular IFI16 protein alone or by synergy with lipopolysaccharide acts like Damage-associated molecular patterns propagating "Danger Signal" through MyD88-dependent TLR-pathway.
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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.