What is it about?
Genetic variants within the ORMDL3 locus carry the highest known risk for childhood asthma. Genetic associations between disease and a drug target more than double the chance of success in Phase II trials. Our results suggest a range of possible therapeutic benefits from accessing ORMDL3-regulated pathways on airway viral infection, inflammation and bronchial responsiveness.
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Why is it important?
We characterized pleiotropic effects of ORMDL3 on lung epithelial cells for the responses to IL-1B stimulation. We observed differentiated expression of genes involved in stress responses, host-pathogen interactions, and ubiquitination due to silence of ORMDL3. Importantly, knockdown of ORMDL3 decreased the expression of pro-inflammatory cytokines and ICAM1, a known receptor for human rhinovirus (HRV). HRV induces wheeze which is the major cause of morbidity in asthmatic children. We also observed that knockdown of ORMDL3 could alter the levels of metabolites integral to glycolysis and increased the levels of the bioactive lipids ceramides and sphinosine-1-phosphate. ORMDL3 has diverse effects on lung epithelial cells and the novel pathways provide potential therapeutic targets in asthma.
Perspectives
I wish this article can make people to think about the powerful approaches with genomic and metabolic platforms in complicated diseases. The observations can reveal the novel links for the disease mechanisms.
Youming Zhang
Imperial College London
Read the Original
This page is a summary of: The ORMDL3 Asthma Gene Regulates ICAM1 and Has Multiple Effects on Cellular Inflammation, American Review of Respiratory Disease, February 2019, American Thoracic Society,
DOI: 10.1164/rccm.201803-0438oc.
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