ArticleThe Journal of biological chemistry2016
DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes: A MECHANISM PROMOTING GLUCOCORTICOID INSENSITIVITY.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Identifying Therapeutic Targets for Bronchial Asthma: Systematic Druggable Genome-Wide Mendelian Randomization.Health science reports · 2026Article
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- Single-cell profiling of African swine fever virus disease in the pig spleen reveals viral and host dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Temperature-induced embryonic diapause in chickens is mediated by PKC-NF-κB-IRF1 signaling.BMC biology · 2023Article
- FOXP1 inhibits pancreatic cancer growth by transcriptionally regulating IRF1 expression.PloS one · 2023Article
- Cellular and transcriptome signatures unveiled by single-cell RNA-Seq followingFrontiers in immunology · 2023Article
- Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis.Frontiers in molecular biosciences · 2022Article
- Potentiation of long-acting βRespiratory research · 2021Article
- Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma.Respiratory research · 2021Article
- Review
- Pleiotropic Effects of Glucocorticoids on the Immune System in Circadian Rhythm and Stress.Frontiers in immunology · 2021Review
- P38 MAPK and glucocorticoid receptor crosstalk in bronchial epithelial cells.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Glucocorticoid-driven transcriptomes in human airway epithelial cells: commonalities, differences and functional insight from cell lines and primary cells.BMC medical genomics · 2019Article
- IRF1 inhibits the proliferation and metastasis of colorectal cancer by suppressing the RAS-RAC1 pathway.Cancer management and research · 2019Article
- Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance.The Journal of biological chemistry · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, mediates dexamethasone-induced repression of MAPKs, 14 of 46 interleukin-1β (IL1B)-induced mRNAs were significantly enhanced by DUSP1 overexpression in pulmonary A549 cells. These include the interferon regulatory factor, IRF1, and the chemokine, CXCL10. Of these, DUSP1-enhanced mRNAs, 10 including CXCL10, were IRF1-dependent. MAPK inhibitors and DUSP1 overexpression prolonged IRF1 expression by elevating transcription and increasing IRF1 mRNA and protein stability. Conversely, DUSP1 silencing increased IL1B-induced MAPK phosphorylation while significantly reducing IRF1 protein expression at 4 h. This confirms a regulatory network whereby DUSP1 switches off MAPKs to maintain IRF1 expression. There was no repression of IRF1 expression by dexamethasone in primary human bronchial epithelial cells, and in A549 cells IL1B-induced IRF1 protein was only modestly and transiently repressed. Although dexamethasone did not repress IL1B-induced IRF1 protein expression at 4-6 h, silencing of IL1B plus dexamethasone-induced DUSP1 significantly reduced IRF1 expression. IL1B-induced expression of CXCL10 was largely insensitive to dexamethasone, whereas other DUSP1-enhanced, IRF1-dependent mRNAs showed various degrees of repression. With IL1B plus dexamethasone, CXCL10 expression was also IRF1-dependent, and expression was reduced by DUSP1 silencing. Thus, IL1B plus dexamethasone-induced DUSP1 maintains expression of IRF1 and the IRF1-dependent gene, CXCL10. This is supported by chromatin immunoprecipitation showing IRF1 recruitment to be essentially unaffected by dexamethasone at the CXCL10 promoter or at the promoters of more highly repressed IRF1-dependent genes. Since IRF1-dependent genes, such as CXCL10, are central to host defense, these data may help explain the reduced effectiveness of glucocorticoids during asthma exacerbations.
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