ArticleAmerican journal of respiratory cell and molecular biology2021
Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells.
Article in American journal of respiratory cell and molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 28 citations in OpenAlex.
- Interferon Regulatory Factors as Potential Therapeutic Targets in Cardiovascular Disease: Focusing on Vascular Inflammation.International journal of molecular sciences · 2026Review
- Mechanistic Investigation of Vitexin in Ameliorating Ovarian Fibrosis in PCOS Mice via the NR4A1/NLRP3 Signaling Pathway.Metabolites · 2026Article
- The ubiquitin ligase FBXW7 regulates epithelial pyroptosis in severe asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Targeting Complement Component 1q Ameliorates Diabetic Endothelial Inflammation Via Orphan Nuclear Receptor 4a1-Dependent Suppression of Nuclear Factor κB Signaling.Journal of the American Heart Association · 2026Article
- The KEAP1/NRF2 axis controls LPS-induced oxidative stress, inflammasome activation and caspase-1 activity in human endothelial cells.PloS one · 2026Article
- A novel role of the TNF-α/p65/IRF1 axis in aggravating rheumatoid arthritis through the induction of fibroblast-like synoviocytes pyroptosis.Frontiers in pharmacology · 2026Article
- Pretreatment with alendronate augments lipid A-induced IFN-β production via upregulation of cGAS expression.Pharmacological reports : PR · 2025Article
- Targeting cholesterol-driven pyroptosis: a promising strategy for the prevention and treatment of atherosclerosis.Molecular biology reports · 2025Review
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Article
- HPGD: An Intermediate Player in Microglial Polarization and Multiple Sclerosis Regulated by Nr4a1.Molecular neurobiology · 2025Article
- CHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy.Communications biology · 2024Article
- Inhibiting endothelial cell Mst1 attenuates acute lung injury in mice.JCI insight · 2024Article
- Chaperone- and PTM-mediated activation of IRF1 tames radiation-induced cell death and the inflammatory response.Cellular & molecular immunology · 2024Article
- Article
- Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis.Immunity, inflammation and disease · 2023Article
- Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet.Current medical science · 2023Article
- The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- New Avenues for Antiinflammatory Signaling of Nur77 in Acute Lung Injury.American journal of respiratory cell and molecular biology · 2021Article
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9 authors at 2 institutions in 2 countries.
Funding
Abstract
Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the innate immune system. Recently, it has been increasingly recognized that aberrant inflammasome activation is critically involved in endothelial dysfunction in a variety of human diseases, such as atherosclerosis, acute lung injury (ALI), and type 2 diabetes. The molecular mechanisms underlying endothelial inflammasome activation, however, have not been completely elucidated. In the present study, we identified orphan nuclear receptor Nur77 as a novel regulator in controlling inflammasome activation in vascular endothelial cells (ECs). We demonstrated that LPS-induced inflammasome activation was significantly inhibited by ectopic overexpression of Nur77, predominantly through transcriptional suppression of caspase-1 expression in vascular ECs. Consistent with this observation, we found that LPS-induced inflammasome activation was significantly augmented in lung ECs isolated from Nur77-knockout mice. Mechanistically, we showed that Nur77-induced inhibition of caspase-1 expression was due to an inhibition of IRF1 (IFN regulatory factor 1) expression and its subsequent binding to the caspase-1 promoter. Importantly, in a mouse model of LPS-induced ALI, Nur77 knockout led to a marked activation of caspase-1 in the lung, increased alveolar and circulating IL-1β levels, and exacerbated ALI, all of which were substantially inhibited by administration of caspase-1 inhibitor. Together, our results support the presence of an important role for Nur77 in controlling inflammasome activation in vascular ECs and suggest that Nur77 could be a novel therapeutic target for the treatment of human diseases associated with aberrant inflammasome activation, such as ALI and atherosclerosis.
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