ArticleJournal of translational medicine2021
Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis.
Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Revisiting down syndrome through the lens of interferonopathy and innate immune dysregulation.Frontiers in immunology · 2026Pooled it
- Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling.Frontiers in immunology · 2022Trial
- FOS regulation of T-cell activation and the mechanism of inflammatory injury of coronary endothelium in Kawasaki disease.Translational pediatrics · 2026Article
- Integrated Bulk and Single-Cell RNA-Seq Analysis Reveals Transcriptional Activation of PTGS2 by FOS in Progression From T2DM to T2DM-Associated NAFLD.Journal of cellular and molecular medicine · 2026Article
- The acid-sensing ion channel 1a modulates anxiety- and depression-related behaviors via its influencing on the activity of corticotropin-releasing hormone-expressing neurons in the hypothalamic paraventricular nucleus in male mice.Translational psychiatry · 2026Article
- Comprehensive transcriptomic and metabolomic analysis provides insight into transportation stress effects on fish muscle quality.NPJ science of food · 2026Article
- FOS Knockdown Alleviates Helicobacter pylori-Infected Gastritis by Suppressing Mast Cell Activation and Treg Polarization.Mediators of inflammation · 2026Article
- Up-regulation of NGEF via the BRAFBiochemistry and biophysics reports · 2025Article
- Spon2 knockdown suppresses the phenotype of house dust mite-induced allergic asthma in mice and cells.Immunologic research · 2025Article
- Integrative multi-omics identifies AP-1 transcription factor as a targetable mediator of acquired osimertinib resistance in non-small cell lung cancer.Cell death & disease · 2025Article
- Sirtuin 2 exacerbates renal tubule injury and inflammation in diabetic mice via deacetylation of c-Jun/c-Fos.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- FOS as a biomarker for myocardial infarction treatment with Deng's Yangxin Decoction: a systems biology-based analysis.Frontiers in cardiovascular medicine · 2025Article
- Article
- Study on the correlation between Interleukin 4 and febrile seizures.CytoJournal · 2025Article
- AP-1 inhibitor induces ferroptosis via the PI3K/AKT pathway in multiple myeloma cells.Heliyon · 2024Article
- scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate.International journal of molecular sciences · 2024Article
- Therapeutic Potential and Mechanisms of Mesenchymal Stem Cell and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Atopic Dermatitis.Journal of inflammation research · 2024Review
- Computational recognition of regulator genes and signature for ferroptosis with implications on immunological properties and clinical management of atopic dermatitis.Frontiers in immunology · 2024Article
- Integration of ATAC-seq and RNA-seq identifies MX1-mediated AP-1 transcriptional regulation as a therapeutic target for Down syndrome.Biological research · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivator protein-1 (AP1), a c-Fos-JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (FcεRI) binding. This study examined c-Fos involvement in MC activation and tested the effects of the c-Fos/AP1 inhibitor T-5224 on MCs activation and allergic responses.
methodsIn vitro studies were conducted with two MC model systems: rat basophilic leukemia cells (RBLs) and mouse bone marrow derived mast cells (BMMCs). MC degranulation and effector functions were examined with β-hexosaminidase release and cytokine secretion assays. c-Fos/AP1 was inhibited with T-5224. c-Fos activity was suppressed with short hairpin RNA targeting c-Fos (shFos). In vivo immune responses were evaluated in passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models, as well as in an oxazolone (OXA)-induced model of atopic dermatitis, a common allergic disease.
resultsc-Fos expression was elevated transcriptionally and translationally in IgE-stimulated MCs. c-Fos binding of the Egr1 (early growth response 1) promoter upregulated Egr1 transcription, leading to production of interleukin (IL)4. T-5224 reduced FcεRI-mediated MC degranulation (evidenced by β-hexosaminidase activity and histamine levels) and diminished EGR1 and IL4 expression. T-5224 attenuated IgE-mediated allergic responses in PCA and ASA models, and it suppressed MC-mediated atopic dermatitis in mice.
conclusionIgE binding can activate MCs via a c-Fos/Egr1/IL-4 axis. T-5224 suppresses MC activation in vitro and in vivo and thus represents a promising potential strategy for targeting MC activation to treat allergic diseases.
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