ArticleJCI insight2024
Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.
Article in JCI insight, 2024. 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, 20 citations in OpenAlex.
- Age-associated loss of lymphatic vessels promotes cardiac inflammation.Nature cardiovascular research · 2026Article
- Spatial transcriptomics reveals coordinated endothelial and epithelial activator protein-1 activation in chronic lung allograft dysfunction.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026Article
- Negative regulation of human IL-33 in endothelium during allergic airway inflammation.JCI insight · 2026Article
- Molecular Links Between Smoking, COPD, and Lung Cancer: A DNA Methylation Perspective.Cancers · 2026Article
- Peritoneal cavity-derived GATA6Journal of advanced research · 2026Article
- Airway epithelial heterogeneity and mucus plugging in asthmatic bronchioles.American journal of respiratory and critical care medicine · 2026Article
- Expression spectrum of TE-driven transcripts in human adult tissues.Genome biology · 2026Article
- Lactate attenuates hepatic ischemia-reperfusion injury by reducing intrahepatic inflammation and suppressing hepatocyte-neutrophil interaction via the IL-33/ST2 pathway.Cell communication and signaling : CCS · 2026Article
- Microbial sensing through the non-canonical inflammasome modulates airway type 2 immunity.Frontiers in immunology · 2026Article
- Ginsenoside Rg1 attenuates asthma features in mice co-exposed to house dust mite allergen and diesel exhaust particle by modulating epithelial ILC2 interactions.Journal of ginseng research · 2026Article
- HSP70 is a chaperone for IL-33 activity in chronic airway disease.JCI insight · 2025Article
- Quantification of single cell-type-specific alternative transcript initiation.bioRxiv : the preprint server for biology · 2025Article
- Proteogenomic verifies targets underlying erythromycin alleviate neutrophil extracellular traps-induced inflammation.Respiratory research · 2025Article
- Innovation through imitation: IL-33 decoys show promise in pulmonary fibrosis.The Journal of pharmacology and experimental therapeutics · 2025Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- IL-33: Friend or foe in transplantation?The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD.
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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.