Pathophysiological regulation of lung function by the free fatty acid receptor FFA4

Rudi Prihandoko; Davinder Kaur; Coen H. Wiegman; Elisa Alvarez-Curto; Chantal Donovan; Latifa Chachi; Trond Ulven; Martha R. Tyas; Eloise Euston; Zhaoyang Dong; Abdulrahman Ghali M. Alharbi; Richard Y. Kim; Jack G. Lowe; Philip M. Hansbro; Kian Fan Chung; Christopher E. Brightling; Graeme Milligan; Andrew B. Tobin

doi:10.1126/scitranslmed.aaw9009

Research ArticleRESPIRATORY DISEASE

Pathophysiological regulation of lung function by the free fatty acid receptor FFA4

View ORCID ProfileRudi Prihandoko¹,
View ORCID ProfileDavinder Kaur²,
View ORCID ProfileCoen H. Wiegman³,
View ORCID ProfileElisa Alvarez-Curto¹,
Chantal Donovan⁴,⁵,
View ORCID ProfileLatifa Chachi²,
View ORCID ProfileTrond Ulven ⁶,
Martha R. Tyas¹,
View ORCID ProfileEloise Euston¹,
View ORCID ProfileZhaoyang Dong¹,
Abdulrahman Ghali M. Alharbi¹,⁷,
Richard Y. Kim⁴,⁵,
View ORCID ProfileJack G. Lowe³,
Philip M. Hansbro ⁴,⁵,
View ORCID ProfileKian Fan Chung ³,
View ORCID ProfileChristopher E. Brightling ²,*,
View ORCID ProfileGraeme Milligan ¹,* and
View ORCID ProfileAndrew B. Tobin ¹,*

¹Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.
²Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, LE3 9QP, Leicester, UK.
³Airway Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
⁴Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW 2305 and The University of Newcastle, Callaghan, NSW 2208, Australia.
⁵Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, and University of Technology Sydney, Faculty of Science, Ultimo NSW 2007, Australia.
⁶Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
⁷Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 42353, Saudi Arabia.

↵*Corresponding author. Email: andrew.tobin{at}glasgow.ac.uk (A.B.T.); graeme.milligan{at}glasgow.ac.uk (G.M.); ceb17{at}le.ac.uk (C.E.B.)

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Science Translational Medicine 19 Aug 2020:
Vol. 12, Issue 557, eaaw9009
DOI: 10.1126/scitranslmed.aaw9009

Rudi Prihandoko

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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Davinder Kaur

2Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, LE3 9QP, Leicester, UK.

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Coen H. Wiegman

3Airway Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.

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Elisa Alvarez-Curto

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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Chantal Donovan

4Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW 2305 and The University of Newcastle, Callaghan, NSW 2208, Australia.

5Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, and University of Technology Sydney, Faculty of Science, Ultimo NSW 2007, Australia.

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Latifa Chachi

2Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, LE3 9QP, Leicester, UK.

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Trond Ulven

6Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

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Martha R. Tyas

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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Eloise Euston

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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Zhaoyang Dong

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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Abdulrahman Ghali M. Alharbi

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

7Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 42353, Saudi Arabia.

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Richard Y. Kim

4Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW 2305 and The University of Newcastle, Callaghan, NSW 2208, Australia.

5Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, and University of Technology Sydney, Faculty of Science, Ultimo NSW 2007, Australia.

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Jack G. Lowe

3Airway Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.

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Philip M. Hansbro

4Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW 2305 and The University of Newcastle, Callaghan, NSW 2208, Australia.

5Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, and University of Technology Sydney, Faculty of Science, Ultimo NSW 2007, Australia.

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Kian Fan Chung

3Airway Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.

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Christopher E. Brightling

2Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, LE3 9QP, Leicester, UK.

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For correspondence: andrew.tobin@glasgow.ac.uk graeme.milligan@glasgow.ac.uk ceb17@le.ac.uk

Graeme Milligan

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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For correspondence: andrew.tobin@glasgow.ac.uk graeme.milligan@glasgow.ac.uk ceb17@le.ac.uk

Andrew B. Tobin

1Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, G12 8QQ, Scotland, UK.

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For correspondence: andrew.tobin@glasgow.ac.uk graeme.milligan@glasgow.ac.uk ceb17@le.ac.uk

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Breathing easy

Asthma and chronic obstructive pulmonary disease result in airway swelling that hinders breathing. Prihandoko et al. found that intranasal delivery of a free fatty acid receptor 4 (FFA4) agonist reduced airway resistance in mouse models of acute and chronic ozone pollution–mediated inflammation as well as house dust mite and cigarette smoke–induced inflammation. This airway relaxation was mediated in part by the release of prostaglandin PGE₂. FFA4 agonism also mediated smooth muscle relaxation of ex vivo human airway samples, suggesting FFA4 as a potential respiratory disease target in humans.

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Pathophysiological regulation of lung function by the free fatty acid receptor FFA4

Breathing easy

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