ArticleThe Journal of biological chemistry2010
TNFα and IFNγ synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-κB, and the transcriptional coactivator CREB-binding protein.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 123 citations in OpenAlex.
- Article
- Identification and Functional Characterization of a Novel Long Non-Coding RNA NLRP14-OT in Turbot (Animals : an open access journal from MDPI · 2026Article
- Targeting macrophage-derived SPP1 enhances CD8 T cell infiltration via ROS-DNA fragment/cGAS-STING/STAT1-mediated CXCL9/10 in tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- The JAK1-STAT1 signaling pathway triggers inflammation responses in chronic obstructive sleep apnea rat model.PloS one · 2026Article
- Macrophage CCL7 promotes resistance to immunotherapy for colorectal cancer by regulating the infiltration of macrophages and CD8Journal for immunotherapy of cancer · 2025Article
- Targeting synergetic endothelial inflammation by inhibiting NFKB and JAK-STAT pathways.iScience · 2025Article
- Anti-PD-1 synergizes with RFA to suppress abscopal tumors and induce durable memory against recurrence in HCC.Liver research (Beijing, China) · 2025Article
- Kynurenine-AhR reduces T-cell infiltration and induces a delayed T-cell immune response by suppressing the STAT1-CXCL9/CXCL10 axis in tuberculosis.Cellular & molecular immunology · 2024Article
- Bioinformatic analysis and experimental validation of the potential gene in the airway inflammation of steroid-resistant asthma.Scientific reports · 2023Article
- Multi-omics delineation of cytokine-induced endothelial inflammatory states.Communications biology · 2023Article
- Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.International journal of molecular sciences · 2022Review
- A Human Skin Model for Assessing Arboviral Infections.JID innovations : skin science from molecules to population health · 2022Article
- Article
- Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy.Molecular therapy oncolytics · 2022Article
- Th1 cytokines synergize to change gene expression and promote corticosteroid insensitivity in pediatric airway smooth muscle.Respiratory research · 2022Article
- CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity.Nature communications · 2022Article
- TNF-α augments CXCL10/CXCR3 axis activity to induce Epithelial-Mesenchymal Transition in colon cancer cell.International journal of biological sciences · 2021Article
- Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx.Molecular & cellular proteomics : MCP · 2021Article
- Alpha-1 antitrypsin deficient individuals have circulating extracellular vesicles with profibrogenic cargo.Cell communication and signaling : CCS · 2020Article
- Important lessons learned from studies on the pharmacology of glucocorticoids in human airway smooth muscle cells: Too much of a good thing may be a problem.Pharmacology & therapeutics · 2020Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Asthmatic airway smooth muscle (ASM) expresses interferon-γ-inducible protein-10 (CXCL10), a chemokine known to mediate mast cell migration into ASM bundles that has been reported in the airways of asthmatic patients. CXCL10 is elevated in patients suffering from viral exacerbations of asthma and in patients with chronic obstructive pulmonary disease (COPD), diseases in which corticosteroids are largely ineffective. IFNγ and TNFα synergistically induce CXCL10 release from human ASM cells in a steroid-insensitive manner, via an as yet undefined mechanism. We report that TNFα activates the classical NF-κB (nuclear factor κB) pathway, whereas IFNγ activates JAK2/STAT-1α and that inhibition of the JAK/STAT pathway is more effective in abrogating CXCL10 release than the steroid fluticasone. The synergy observed with TNFα and IFNγ together, however, did not lie at the level of NF-κB activation, STAT-1α phosphorylation, or in vivo binding of these transcription factors to the CXCL10 promoter. Stimulation of human ASM cells with TNFα and IFNγ induced histone H4 but not histone H3 acetylation at the CXCL10 promoter, although no synergism was observed when both cytokines were combined. We show, however, that TNFα and IFNγ exert a synergistic effect on the recruitment of CREB-binding protein (CBP) to the CXCL10, which is accompanied by increased RNA polymerase II. Our results provide evidence that synergism between TNFα and IFNγ lies at the level of coactivator recruitment in human ASM and suggest that inhibition of JAK/STAT signaling may be of therapeutic benefit in steroid-resistant airway disease.
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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.