ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Glucocorticoid and TNF signaling converge at A20 (TNFAIP3) to repress airway smooth muscle cytokine expression.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Co-administration of 5α-reductase Inhibitors Worsens the Adverse Metabolic Effects of Prescribed Glucocorticoids.The Journal of clinical endocrinology and metabolism · 2020Trial
- Dynamic remodeling of the pancreas immune landscape in obesity.Nature communications · 2026Article
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Abi1 mediates airway smooth muscle cell proliferation and airway remodeling via Jak2/STAT3 signaling.iScience · 2022Article
- Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks.Drug delivery · 2021Article
- Insights into glucocorticoid responses derived from omics studies.Pharmacology & therapeutics · 2021Review
- Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19.Frontiers in pharmacology · 2021Article
- Article
- 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
- Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases.Scientific reports · 2020Article
- Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring.Nutrients · 2019Article
- Nascent transcript analysis of glucocorticoid crosstalk with TNF defines primary and cooperative inflammatory repression.Genome research · 2019Article
- Th1 cytokines TNF-α and IFN-γ promote corticosteroid resistance in developing human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Glucocorticoid Receptor ChIP-Seq Identifies PLCD1 as a KLF15 Target that Represses Airway Smooth Muscle Hypertrophy.American journal of respiratory cell and molecular biology · 2017Article
- Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance.The Journal of biological chemistry · 2017Review
- Long-acting βAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes: A MECHANISM PROMOTING GLUCOCORTICOID INSENSITIVITY.The Journal of biological chemistry · 2016Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Airway smooth muscle is a major target tissue for glucocorticoid (GC)-based asthma therapies, however, molecular mechanisms through which the GC receptor (GR) exerts therapeutic effects in this key airway cell type have not been fully elucidated. We previously identified the nuclear factor-κB (NF-κB) inhibitor, A20 (TNFAIP3), as a mediator of cytokine repression by glucocorticoids (GCs) in airway epithelial cells and defined cooperative regulation of anti-inflammatory genes by GR and NF-κB as a key mechanistic underpinning of airway epithelial GR function. Here, we expand on these findings to determine whether a similar mechanism is operational in human airway smooth muscle (HASM). Using HASM cells derived from normal and fatal asthma samples as an in vitro model, we demonstrate that GCs spare or augment TNF-mediated induction of A20 (TNFAIP3), TNIP1, and NFKBIA, all implicated in negative feedback control of NF-κB-driven inflammatory processes. We applied chromatin immunoprecipitation and reporter analysis to show that GR and NF-κB directly regulate A20 expression in HASM through cooperative induction of an intronic enhancer. Using overexpression, we show for the first time that A20 and its interacting partner, TNIP1, repress TNF signaling in HASM cells. Moreover, we applied small interfering RNA-based gene knockdown to demonstrate that A20 is required for maximal cytokine repression by GCs in HASM. Taken together, our data suggest that inductive regulation of A20 by GR and NF-κB contributes to cytokine repression in HASM.
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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.