Imperial College London
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Professor William Cookson

Faculty of Medicine, National Heart & Lung Institute

Professor of Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 2943w.cookson

 
 
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Location

 

400Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Laura:2021:10.1186/s12890-021-01496-5,
author = {Laura, G and Liu, Y and Fernandes, K and Willis-Owen, SAG and Ito, K and Cookson, WO and Moffatt, MF and Zhang, Y},
doi = {10.1186/s12890-021-01496-5},
journal = {BMC Pulmonary Medicine},
title = {ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells},
url = {http://dx.doi.org/10.1186/s12890-021-01496-5},
volume = {21},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:Oroscomucoid 3 (ORMDL3) has been linked to susceptibility of childhood asthma and respiratory viral infection. Polyinosinic-polycytidylic acid (poly I:C) is a synthetic analog of viral double-stranded RNA, a toll-like receptor 3 (TLR3) ligand and mimic of viral infection.Methods:To investigate the functional role of ORMDL3 in the poly I:C-induced inflammatory response in airway epithelial cells, ORMDL3 knockdown and over-expression models were established in human A549 epithelial cells and primary normal human bronchial epithelial (NHBE) cells. The cells were stimulated with poly I:C or the Th17 cytokine IL-17A. IL-6 and IL-8 levels in supernatants,  mRNA levels of genes in the TLR3 pathway and inflammatory response from cell pellets were measured. ORMDL3 knockdown models in A549 and BEAS-2B epithelial cells were then infected with live human rhinovirus (HRV16) followed by IL-6 and IL-8 measurement.Results:ORMDL3 knockdown and over-expression had little influence on the transcript levels of TLR3 in airway epithelial cells. Time course studies showed that ORMDL3-deficient A549 and NHBE cells had an attenuated IL-6 and IL-8 response to poly I:C stimulation. A549 and NHBE cells over-expressing ORMDL3 released relatively more IL-6 and IL-8 following poly I:C stimulation. IL-17A exhibited a similar inflammatory response in ORMDL3 knockdown and over-expressing cells, but co-stimulation of poly I:C and IL-17A did not significantly enhance the IL-6 and IL-8 response. Transcript abundance of IFNB following poly I:C stimulation was not significantly altered by ORMDL3 knockdown or over-expression. Dampening of the IL-6 response by ORMDL3 knockdown was confirmed in HRV16 infected BEAS-2B and A549 cells.Conclusions:ORMDL3 regulates the viral inflammatory response in airway epithelial cells via mechanisms independent of the TLR3 pathway.
AU  - Laura,G
AU  - Liu,Y
AU  - Fernandes,K
AU  - Willis-Owen,SAG
AU  - Ito,K
AU  - Cookson,WO
AU  - Moffatt,MF
AU  - Zhang,Y
DO  - 10.1186/s12890-021-01496-5
PY  - 2021///
SN  - 1471-2466
TI  - ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells
T2  - BMC Pulmonary Medicine
UR  - http://dx.doi.org/10.1186/s12890-021-01496-5
UR  - http://hdl.handle.net/10044/1/89387
VL  - 21
ER  -
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