ArticleAmerican journal of respiratory and critical care medicine2019
The ORMDL3 Asthma Gene Regulates ICAM1 and Has Multiple Effects on Cellular Inflammation.
Article in American journal of respiratory and critical care medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Genetic and environmental risk factors of asthma: a narrative review.Frontiers in immunology · 2026Pooled it
- Decreased sphingolipid synthesis in children with 17q21 asthma-risk genotypes.The Journal of clinical investigation · 2020Trial
- Differential associations of allergic disease genetic variants with developmental profiles of eczema, wheeze and rhinitis.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2019Trial
- Unmasking programmed cell death in rhinovirus-driven asthma pathology.Biochemical Society transactions · 2026Review
- Novel immune-related susceptibility loci associated with pediatric steroid-sensitive nephrotic syndrome identified by a transethnic genome-wide association study.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Genetic Evidence for Unified Airway Disease: Shared Epithelial and Immune Architecture Across Major Airway Diseases.International journal of molecular sciences · 2026Article
- From gut microbiota dysbiosis to immune dysregulation: pathogenic mechanisms and emerging therapeutic perspectives in pediatric asthma.Frontiers in immunology · 2026Review
- Review
- Orm2 promotes nitrogen-induced sphingolipid production and endocytosis via Orm1 phosphorylation.Journal of lipid research · 2025Article
- Supplementary Feeding Regulates Muscle Development of Oula Sheep (Tibetan Sheep,Animals : an open access journal from MDPI · 2025Article
- Integration of multi-source gene interaction networks and omics data with graph attention networks to identify novel disease genes.Bioinformatics (Oxford, England) · 2025Article
- MAP3K8 is a potential therapeutic target in airway epithelial inflammation.Journal of inflammation (London, England) · 2024Article
- Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signalling and airway inflammation.The European respiratory journal · 2024Article
- Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.BMC medicine · 2024Article
- Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.eLife · 2024Article
- ORMDL3 regulates NLRP3 inflammasome activation by maintaining ER-mitochondria contacts in human macrophages and dictates ulcerative colitis patient outcome.The Journal of biological chemistry · 2024Article
- Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells.Frontiers in immunology · 2024Article
- The functional role of CST1 and CCL26 in asthma development.Immunity, inflammation and disease · 2024Article
- Common Pathogeneses Underlying Asthma and Chronic Obstructive Pulmonary Disease -Insights from Genetic Studies.International journal of chronic obstructive pulmonary disease · 2024Review
- From gene identifications to therapeutic targets for asthma: Focus on great potentials ofChinese medical journal pulmonary and critical care medicine · 2023Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
rationalePolymorphisms on chromosome 17q21 confer the major genetic susceptibility to childhood-onset asthma. Risk alleles positively correlate with ORMDL3 (orosomucoid-like 3) expression. The locus influences disease severity and the frequency of human rhinovirus (HRV)-initiated exacerbations. ORMDL3 is known to regulate sphingolipid synthesis by binding serine palmitoyltransferase, but its role in inflammation is incompletely understood.
objectivesTo investigate the role of ORMDL3 in cellular inflammation.
methodsWe modeled a time series of IL1B-induced inflammation in A549 cells, using cytokine production as outputs and testing effects of ORMDL3 siRNA knockdown, ORMDL3 overexpression, and the serine palmitoyltransferase inhibitor myriocin. We replicated selected findings in normal human bronchial epithelial cells. Cytokine and metabolite levels were analyzed by analysis of variance. Transcript abundances were analyzed by group means parameterization, controlling the false discovery rate below 0.05. MEASUREMENTS AND MAIN
resultsSilencing ORMDL3 led to steroid-independent reduction of IL6 and IL8 release and reduced endoplasmic reticulum stress after IL1B stimulation. Overexpression and myriocin conversely augmented cytokine release. Knockdown reduced expression of genes regulating host-pathogen interactions, stress responses, and ubiquitination: in particular, ORMDL3 knockdown strongly reduced expression of the HRV receptor ICAM1. Silencing led to changes in levels of transcripts and metabolites integral to glycolysis. Increased levels of ceramides and the immune mediator sphingosine-1-phosphate were also observed.
conclusionsThe results show ORMDL3 has pleiotropic effects during cellular inflammation, consistent with its substantial genetic influence on childhood asthma. Actions on ICAM1 provide a mechanism for the locus to confer susceptibility to HRV-induced 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.