ArticleThe Journal of allergy and clinical immunology2015
Aberrant ORM (yeast)-like protein isoform 3 (ORMDL3) expression dysregulates ceramide homeostasis in cells and ceramide exacerbates allergic asthma in mice.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 110 citations in OpenAlex.
- Decreased sphingolipid synthesis in children with 17q21 asthma-risk genotypes.The Journal of clinical investigation · 2020Trial
- Sphingomyelin synthase 2 deficiency suppresses airway mucus accumulation by altering sphingolipid flux and mucin glycosylation.Molecular and cellular biochemistry · 2026Article
- Genetic Evidence for Unified Airway Disease: Shared Epithelial and Immune Architecture Across Major Airway Diseases.International journal of molecular sciences · 2026Article
- ORMDL3 as Key Regulator of Endothelial Dysfunction in Atherosclerosis via Sphingolipid Biosynthesis.Inflammation · 2026Article
- Neonatal sevoflurane exposure disrupts the lung-brain axis and drives microglial neuroinflammation and cognitive deficits.Journal of neuroinflammation · 2026Article
- Sex hormones influence ORMDL3 expression: Implications for sex-associated asthma phenotype.The Journal of allergy and clinical immunology · 2026Article
- Metabolic licensing at the dendritic cell-NK cells immune synapse in viral asthma exacerbations.Frontiers in immunology · 2026Review
- Linking Lipid Metabolism and Immune Function: New Insights into Chronic Respiratory Diseases.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Fingolimod, a sphingosine-1-phosphate receptor modulator, prevents neonatal bronchopulmonary dysplasia and subsequent airway remodeling in a murine model.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Association between nasopharyngeal airway lipidome signatures of infants with severe bronchiolitis and risk of recurrent wheeze: A prospective multicenter cohort study.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2024Article
- Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.International journal of molecular sciences · 2024Review
- Article
- Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors.Allergy · 2024Article
- New Therapeutic Options in Pulmonal Diseases: Sphingolipids and Modulation of Sphingolipid Metabolism.Handbook of experimental pharmacology · 2024Review
- Simultaneous deletion of ORMDL1 and ORMDL3 proteins disrupts immune cell homeostasis.Frontiers in immunology · 2024Article
- Genetic correlation between chronic sinusitis and autoimmune diseases.Frontiers in allergy · 2024Article
- Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study.Metabolites · 2023Article
- From gene identifications to therapeutic targets for asthma: Focus on great potentials ofChinese medical journal pulmonary and critical care medicine · 2023Review
- Nasal Transcriptome and Epigenome Analysis Identifies the Pathogenic Features of Aspirin-Exacerbated Respiratory Disease.Allergy, asthma & immunology research · 2023Article
- Simultaneous reduction of all ORMDL proteins decreases the threshold of mast cell activation.Scientific reports · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAsthma, a chronic inflammatory condition defined by episodic shortness of breath with expiratory wheezing and cough, is a serious health concern affecting more than 250 million persons. Genome-wide association studies have identified ORM (yeast)-like protein isoform 3 (ORMDL3) as a gene associated with susceptibility to asthma. Although its yeast ortholog is a negative regulator of de novo ceramide biosynthesis, how ORMDL3 contributes to asthma pathogenesis is not known.
objectivesWe sought to decipher the molecular mechanism for the pathologic functions of ORMDL3 in asthma and the relationship to its evolutionarily conserved role in regulation of ceramide homeostasis.
methodsWe determined the relationship between expression of ORMDL3 and ceramide in epithelial and inflammatory cells and in asthma pathogenesis in mice.
resultsAlthough small increases in ORMDL3 expression decrease ceramide levels, remarkably, higher expression in lung epithelial cells and macrophages in vitro and in vivo increased ceramide production, which promoted chronic inflammation, airway hyperresponsiveness, and mucus production during house dust mite-induced allergic asthma. Moreover, nasal administration of the immunosuppressant drug FTY720/fingolimod reduced ORMDL3 expression and ceramide levels and mitigated airway inflammation and hyperreactivity and mucus hypersecretion in house dust mite-challenged mice.
conclusionsOur findings demonstrate that overexpression of ORMDL3 regulates ceramide homeostasis in cells in a complex manner and suggest that local FTY720 administration might be a useful therapeutic intervention for the control of allergic asthma.
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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.