ArticleAmerican journal of physiology. Lung cellular and molecular physiology2019
Th1 cytokines TNF-α and IFN-γ promote corticosteroid resistance in developing human airway smooth muscle.
Article in American journal of physiology. Lung cellular and molecular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 63 citations in OpenAlex.
- Immune function in X-linked retinoschisis subjects in an AAV8-RS1 phase I/IIa gene therapy trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Trial
- Article
- Breaking the bottleneck of asthma treatment: the future of omni-targeted therapy.Journal of advanced research · 2026Review
- Multicellular crosstalk in neutrophilic asthma: unraveling the pathogenic web of steroid resistance and emerging precision therapies.Journal of translational medicine · 2026Review
- Targeting Type 2 and Non-type 2 Asthma: Emerging Biologics and Personalized Strategies.Current allergy and asthma reports · 2026Review
- The Airway Epithelial Barrier in Childhood Asthma: A Central Player in Glucocorticoid Therapy, Resistance, and Severe Asthma.Pediatric discovery · 2026Review
- Asthma endotypes and theratypes.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Hypothesis-driven salvage therapy with corticosteroids, tofacitinib, and nintedanib for progressive radiation pneumonitis with possible immune-mediated contribution: a case report.Frontiers in immunology · 2026Article
- Factor Analysis-Based Quantitative Endotyping Improves Associations With CRS Cross-Sectional and Longitudinal Outcomes.International forum of allergy & rhinology · 2026Article
- Reprogrammed MDSCs promote Th1-dominant antitumour response via CD40 induced by autocrine TNF-α after combining cryo-thermal therapy with IL6 and IL17A neutralization.Clinical and translational medicine · 2025Article
- Molecular and Immunomodulatory Mechanisms of Statins in Inflammation and Cancer Therapeutics with Emphasis on the NF-κB, NLRP3 Inflammasome, and Cytokine Regulatory Axes.International journal of molecular sciences · 2025Review
- Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model.Biomedicines · 2025Article
- Inflammation in Asthma: Mechanistic Insights and the Role of Biologics in Therapeutic Frontiers.Biomedicines · 2025Review
- Emerging Concepts in Cytokine Regulation of Airway Remodeling in Asthma.Immunological reviews · 2025Review
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Pharmacogenomic Study of SARS-CoV-2 Treatments: Identifying Polymorphisms Associated with Treatment Response in COVID-19 Patients.Biomedicines · 2025Article
- Aging, brain-derived neurotrophic factor, and allergen-induced pulmonary responses in mice.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Immunological factors, important players in the development of asthma.BMC immunology · 2024Review
- Article
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 3 institutions in 1 country.
Funding
Abstract
Corticosteroids (CSs) are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show CS resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previous studies have demonstrated that Th1 cytokines, such as TNF-α and IFN-γ, promote CS resistance in adult human airway smooth muscle (ASM). In the present study, using a human fetal ASM cell model, we tested the hypothesis that TNF-α/IFN-γ induces CS resistance. In contrast to TNF-α or IFN-γ alone, the combination of TNF-α/IFN-γ blunted the ability of fluticasone propionate (FP) to reduce expression of the chemokines CCL5 and CXCL10 despite expression of key anti-inflammatory glucocorticoid receptor target genes being largely unaffected by TNF-α/IFN-γ. Expression of the NF-κB subunit p65 and phosphorylation of Stat1 were elevated in cells treated with TNF-α/IFN-γ, an effect that remained in the presence of FP. siRNA knockdown studies demonstrated the effects of TNF-α/IFN-γ on increased p65 are mediated by Stat1, a transcription factor activated by IFN-γ. Expression of TNFAIP3, a negative regulator of NF-κB activity, was not altered by TNF-α/IFN-γ. However, the effects of TNF-α/IFN-γ were partially reduced by overexpression of TNFAIP3 but did not influence p65 expression. Together, these data suggest that IFN-γ augments the effects of TNF-α on chemokines by enhancing expression of key inflammatory pathways in the presence of CS. Interactions between TNF-α- and IFN-γ-mediated pathways may promote inflammation in asthmatic children resistant to CSs.
Indexed as
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.