ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
IFN-γ-induced JAK/STAT, but not NF-κB, signaling pathway is insensitive to glucocorticoid in airway epithelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. 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
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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.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Phase 2a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of londamocitinib (AZD4604) two times per day for 12 weeks in adult patients with moderate-to-severe asthma uncontrolled on medium-high-dose ICS-LABA.BMJ open respiratory research · 2026Trial
- AZD0449, an inhaled JAK1 inhibitor, in healthy participants and patients with mild asthma.British journal of clinical pharmacology · 2026Trial
- Stage-Specific Reconstruction of Genome-Wide Genetic and Epigenetic Regulatory Networks Reveals Mechanistic Insights into Asthma Progression.International journal of molecular sciences · 2026Article
- T1-T2 Interplay in the Complex Immune Landscape of Severe Asthma.Immunological reviews · 2025Review
- Glucocorticoid Insensitivity in Severe Asthma: Underlying Molecular Mechanisms, Challenges, and Emerging Therapies.Archives of internal medicine research · 2025Article
- SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2.Frontiers in immunology · 2024Article
- CCL5 is a potential bridge between type 1 and type 2 inflammation in asthma.The Journal of allergy and clinical immunology · 2023Article
- Pulmonary IFN-γ Causes Lymphocytic Inflammation and Cough Hypersensitivity by Increasing the Number of IFN-γ-Secreting T Lymphocytes.Allergy, asthma & immunology research · 2022Article
- Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.Pulmonary therapy · 2022Article
- GP96 and SMP30 Protein Priming of Dendritic Cell Vaccination Induces a More Potent CTL Response against Hepatoma.Journal of healthcare engineering · 2022Article
- Dual role for CXCR3 and CCR5 in asthmatic type 1 inflammation.The Journal of allergy and clinical immunology · 2022Article
- Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability.Frontiers in pharmacology · 2022Article
- Inflammatory activation of surface molecule shedding by upregulation of the pseudoprotease iRhom2 in colon epithelial cells.Scientific reports · 2021Article
- Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma.Advances in experimental medicine and biology · 2021Article
- miR-135a inhibits airway inflammatory response in asthmatic mice via regulating JAK/STAT signaling pathway.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- Mechanism and biomarkers in aortitis--a review.Journal of molecular medicine (Berlin, Germany) · 2020Review
- [Pathogenesis of steroid-resistant asthma and the influence of vitamin D].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Review
- Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration.Disease models & mechanisms · 2019Article
- Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias.JCI insight · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Although the majority of patients with asthma are well controlled by inhaled glucocorticoids (GCs), patients with severe asthma are poorly responsive to GCs. This latter group is responsible for a disproportionate share of health care costs associated with asthma. Recent studies in immune cells have incriminated interferon-γ (IFN-γ) as a possible trigger of GC insensitivity in severe asthma; however, little is known about the role of IFN-γ in modulating GC effects in other clinically relevant nonimmune cells, such as airway epithelial cells. We hypothesized that IFN-γ-induced JAK/STAT-associated signaling pathways in airway epithelial cells are insensitive to GCs and that strategies aimed at inhibiting JAK/STAT pathways can restore steroid responsiveness. Using Western blot analysis we found that all steps of the IFN-γ-induced JAK/STAT signaling pathway were indeed GC insensitive. Transfection of cells with reporter plasmid showed IFN-γ-induced STAT1-dependent gene transcription to be also GC insensitive. Interestingly, real-time PCR analysis showed that IFN-γ-inducible genes (IIGs) were differentially affected by GC, with CXCL10 being GC sensitive and CXCL11 and IFIT2 being GC insensitive. Further investigation showed that the differential sensitivity of IIGs to GC was due to their variable dependency to JAK/STAT vs. NF-κB signaling pathways with GC-sensitive IIGs being more NF-κB dependent and GC-insensitive IIGs being more JAK/STAT dependent. Importantly, transfection of cells with siRNA-STAT1 was able to restore steroid responsiveness of GC-insensitive IIGs. Taken together, our results show the insensitivity of IFN-γ-induced JAK/STAT signaling pathways to GC effects in epithelial cells and also suggest that targeting STAT1 could restore GC responsiveness in patients with severe asthma.
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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.