ArticleJournal of inflammation (London, England)2010
Fas (CD95) induces rapid, TLR4/IRAK4-dependent release of pro-inflammatory HMGB1 from macrophages.
Article in Journal of inflammation (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Innate Immune Sensors and Cell Death-Frontiers Coordinating Homeostasis, Immunity, and Inflammation in Skin.Viruses · 2025Review
- Nerolidol-potential Therapeutic Agent for Various Neurological DisordersCurrent pharmaceutical biotechnology · 2025Review
- FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury.Journal of burn care & research : official publication of the American Burn Association · 2024Article
- Macrophage-Targeted Nanomedicines for ARDS/ALI: Promise and Potential.Inflammation · 2022Review
- Damage-associated Molecular Patterns in Clinical and Animal Models of Uveitis.Ocular immunology and inflammation · 2022Article
- A significant association between CXCL10 -1447 A > G and IL18 -607 C > A gene polymorphism with human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran.Journal of neurovirology · 2021Article
- Article
- A Novel Subset of CD95Frontiers in immunology · 2020Article
- Article
- Decoy Receptor 3 Promotes Preosteoclast Cell Death via Reactive Oxygen Species-Induced Fas Ligand Expression and the IL-1Mediators of inflammation · 2020Article
- Funerals and Feasts: The Immunological Rites of Cell Death.The Yale journal of biology and medicine · 2019Review
- Necrostatin-1 Protects Against D-Galactosamine and Lipopolysaccharide-Induced Hepatic Injury by Preventing TLR4 and RAGE Signaling.Inflammation · 2017Article
- Article
- Critical role of RAGE and HMGB1 in inflammatory heart disease.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- HMGB1 release triggered by the interaction of live retinal cells and uveitogenic T cells is Fas/FasL activation-dependent.Journal of neuroinflammation · 2015Article
- Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.PloS one · 2015Article
- Necroptotic signaling in adaptive and innate immunity.Seminars in cell & developmental biology · 2014Review
- HMGB1 is an early and critical mediator in an animal model of uveitis induced by IRBP-specific T cells.Journal of leukocyte biology · 2014Article
- Fas (CD95) expression in myeloid cells promotes obesity‐induced muscle insulin resistance.EMBO molecular medicine · 2014Article
- Abnormal expression of Toll-like receptor 4 is associated with susceptibility to ethanol-induced gastric mucosal injury in mice.Digestive diseases and sciences · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although Fas (CD95) is recognized as a death receptor that induces apoptosis, recent studies indicate that the Fas/FasL system can induce pro-inflammatory cytokine production by macrophages independent of conventional caspase-mediated apoptotic signaling. The precise mechanism(s) by which Fas activates macrophage inflammation is unknown. We hypothesized that Fas stimulates rapid release of high mobility group box 1 (HMGB1) that acts in an autocrine and/or paracrine manner to stimulate pro-inflammatory cytokine production via a Toll-like receptor-4 (TLR4)/Interleukin-1 receptor associated kinase-4 (IRAK4)-dependent mechanism. Following Fas activation, HMGB1 was released within 1 hr from viable RAW267.4 cells and primary murine peritoneal macrophages. HMGB1 release was more rapid following Fas activation compared to LPS stimulation. Neutralization of HMGB1 with an inhibitory anti-HMGB1 monoclonal antibody strongly inhibited Fas-induced production of tumor necrosis factor (TNF) and macrophage inflammatory protein-2 (MIP-2). Both Fas-induced HMGB1 release and associated pro-inflammatory cytokine production were significantly decreased from Tlr4-/- and Irak4-/- macrophages, but not Tlr2-/- macrophages. These findings reveal a novel mechanism underlying Fas-mediated pro-inflammatory physiological responses in macrophages. We conclude that Fas activation induces rapid, TLR4/IRAK4-dependent release of HMGB1 that contributes to Fas-mediated pro-inflammatory cytokine production by viable macrophages.
Identifiers
What OpenQuestion holds
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.