ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells
Abstract 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...
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doaj-8a49f98f2be248f69b70ec796017d84a2021-05-23T11:27:46ZengBMCBMC Pulmonary Medicine1471-24662021-05-0121111310.1186/s12890-021-01496-5ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cellsGemma Laura0Yi Liu1Kieran Fernandes2Saffron A. G. Willis-Owen3Kazuhiro Ito4William O. Cookson5Miriam F. Moffatt6Youming Zhang7National Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonAbstract 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.https://doi.org/10.1186/s12890-021-01496-5ORMDL3Poly I:CTLR3Epithelial cellInflammatory response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gemma Laura Yi Liu Kieran Fernandes Saffron A. G. Willis-Owen Kazuhiro Ito William O. Cookson Miriam F. Moffatt Youming Zhang |
spellingShingle |
Gemma Laura Yi Liu Kieran Fernandes Saffron A. G. Willis-Owen Kazuhiro Ito William O. Cookson Miriam F. Moffatt Youming Zhang ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells BMC Pulmonary Medicine ORMDL3 Poly I:C TLR3 Epithelial cell Inflammatory response |
author_facet |
Gemma Laura Yi Liu Kieran Fernandes Saffron A. G. Willis-Owen Kazuhiro Ito William O. Cookson Miriam F. Moffatt Youming Zhang |
author_sort |
Gemma Laura |
title |
ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells |
title_short |
ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells |
title_full |
ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells |
title_fullStr |
ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells |
title_full_unstemmed |
ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells |
title_sort |
ormdl3 regulates poly i:c induced inflammatory responses in airway epithelial cells |
publisher |
BMC |
series |
BMC Pulmonary Medicine |
issn |
1471-2466 |
publishDate |
2021-05-01 |
description |
Abstract 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. |
topic |
ORMDL3 Poly I:C TLR3 Epithelial cell Inflammatory response |
url |
https://doi.org/10.1186/s12890-021-01496-5 |
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