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Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection

Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection
Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection
Lipids and their mediators have important regulatory functions in many cellular processes, including the innate antiviral response. The aim of this study was to compare the lipid membrane composition of in vitro differentiated primary bronchial epithelial cells (PBECs) with ex vivo bronchial brushings and to establish whether any changes in the lipid membrane composition affect antiviral defence of cells from donors without and with severe asthma.
Using mass spectrometry, we showed that the lipid membrane of in vitro differentiated PBECs was deprived of polyunsaturated fatty acids (PUFAs) compared to ex vivo bronchial brushings. Supplementation of the culture medium with arachidonic acid (AA) increased the PUFA-content to more closely match the ex vivo membrane profile. Rhinovirus (RV16) infection of AA-supplemented cultures from healthy donors resulted in significantly reduced viral replication while release of inflammatory mediators and prostaglandin E2 (PGE2) was significantly increased. Indomethacin, an inhibitor of prostaglandin-endoperoxide synthases, suppressed RV16-induced PGE2 release and significantly reduced CXCL-8/IL-8 release from AA-supplemented cultures indicating a link between PGE2 and CXCL8/IL-8 release. In contrast, in AA-supplemented cultures from severe asthmatic donors, viral replication was enhanced whereas PTGS2 expression and PGE2 release were unchanged and CXCL8/IL-8 was significantly reduced in response to RV16 infection.
While the PTGS2/COX-2 pathway is initially pro-inflammatory, its downstream products can promote symptom resolution. Thus, reduced PGE2 release during an RV-induced severe asthma exacerbation may lead to prolonged symptoms and slower recovery. Our data highlight the importance of reflecting the in vivo lipid profile in in vitro cell cultures for mechanistic studies.
Bronchial epithelium, arachidonic acid, membrane lipids, rhinovirus, severe asthma
2168-8370
Panchal, Madhuriben H.
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Swindle, Emily J.
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Pell, Theresa J.
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Rowan, Wendy C.
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Childs, Caroline E.
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Thompson, James
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Nicholas, Benjamin L.
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Djukanovic, Ratko
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Goss, Victoria M.
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Postle, Anthony D.
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Davies, Donna E.
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Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
et al.
Panchal, Madhuriben H.
ad071572-6895-48e7-a3d0-5cf07cff9987
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Pell, Theresa J.
a6478e33-eb55-45ed-a1f7-6580af249f56
Rowan, Wendy C.
481c21b7-a63e-40ae-8208-de9b495cfe64
Childs, Caroline E.
ea17ccc1-2eac-4f67-96c7-a0c4d9dfd9c5
Thompson, James
a0a1e940-d720-47de-81d7-ebcd48738239
Nicholas, Benjamin L.
785c44fb-6536-4189-803b-4545425e9385
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Goss, Victoria M.
ef02be5d-9318-4f7d-b076-3153555980d0
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b

Panchal, Madhuriben H., Swindle, Emily J. and Pell, Theresa J. , et al. (2024) Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection. Tissue Barriers, [2300580]. (doi:10.1080/21688370.2023.2300580). (In Press)

Record type: Article

Abstract

Lipids and their mediators have important regulatory functions in many cellular processes, including the innate antiviral response. The aim of this study was to compare the lipid membrane composition of in vitro differentiated primary bronchial epithelial cells (PBECs) with ex vivo bronchial brushings and to establish whether any changes in the lipid membrane composition affect antiviral defence of cells from donors without and with severe asthma.
Using mass spectrometry, we showed that the lipid membrane of in vitro differentiated PBECs was deprived of polyunsaturated fatty acids (PUFAs) compared to ex vivo bronchial brushings. Supplementation of the culture medium with arachidonic acid (AA) increased the PUFA-content to more closely match the ex vivo membrane profile. Rhinovirus (RV16) infection of AA-supplemented cultures from healthy donors resulted in significantly reduced viral replication while release of inflammatory mediators and prostaglandin E2 (PGE2) was significantly increased. Indomethacin, an inhibitor of prostaglandin-endoperoxide synthases, suppressed RV16-induced PGE2 release and significantly reduced CXCL-8/IL-8 release from AA-supplemented cultures indicating a link between PGE2 and CXCL8/IL-8 release. In contrast, in AA-supplemented cultures from severe asthmatic donors, viral replication was enhanced whereas PTGS2 expression and PGE2 release were unchanged and CXCL8/IL-8 was significantly reduced in response to RV16 infection.
While the PTGS2/COX-2 pathway is initially pro-inflammatory, its downstream products can promote symptom resolution. Thus, reduced PGE2 release during an RV-induced severe asthma exacerbation may lead to prolonged symptoms and slower recovery. Our data highlight the importance of reflecting the in vivo lipid profile in in vitro cell cultures for mechanistic studies.

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Panchal_et_al_accepted_manuscript - Accepted Manuscript
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Accepted/In Press date: 2024
Additional Information: Funding Information: CB received a University of Southampton Career Track Award that was part funded by GSK plc. TJP and WCR are employees of GSK plc. DED and RD are co-founders, shareholders and consultants to the university spin-off company Synairgen, which is developing inhaled IFN-β for the treatment of respiratory viral infections. Other authors declare no competing interests. The manuscript was conceived and written by the University of Southampton co-authors and was approved by co-authors from GSK plc. Funding Information: We thank our volunteers who donated airway cells for this study. We thank Alice J. Eminton for technical support. This project was supported by the National Institute for Health Research (NIHR) Southampton Biomedical Research Centre (BRC), and the Asthma, Allergy and Inflammation Research (AAIR) Charity. Publisher Copyright: © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
Keywords: Bronchial epithelium, arachidonic acid, membrane lipids, rhinovirus, severe asthma
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Identifiers

Local EPrints ID: 485905
URI: http://eprints.soton.ac.uk/id/eprint/485905
DOI: doi:10.1080/21688370.2023.2300580
ISSN: 2168-8370
PURE UUID: 618af4f5-33d9-42ae-99ff-f52a8fbad1c4
ORCID for Emily J. Swindle: ORCID iD orcid.org/0000-0003-3644-7747
ORCID for Caroline E. Childs: ORCID iD orcid.org/0000-0001-6832-224X
ORCID for James Thompson: ORCID iD orcid.org/0000-0002-9285-1317
ORCID for Benjamin L. Nicholas: ORCID iD orcid.org/0000-0003-1467-9643
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Cornelia Blume: ORCID iD orcid.org/0000-0001-6133-7318

Catalogue record

Date deposited: 04 Jan 2024 01:38
Last modified: 18 Mar 2024 03:25

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Contributors

Author: Madhuriben H. Panchal
Author: Emily J. Swindle ORCID iD
Author: Theresa J. Pell
Author: Wendy C. Rowan
Author: Caroline E. Childs ORCID iD
Author: James Thompson ORCID iD
Author: Benjamin L. Nicholas ORCID iD
Author: Ratko Djukanovic ORCID iD
Author: Victoria M. Goss
Author: Anthony D. Postle ORCID iD
Author: Donna E. Davies ORCID iD
Author: Cornelia Blume ORCID iD
Corporate Author: et al.

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