Imperial College London
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DR COEN WIEGMAN

Faculty of Medicine, National Heart & Lung Institute

Senior Teaching Fellow
 
 
 
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Contact

 

+44 (0)20 7594 1980c.wiegman

 
 
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Location

 

305Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Prihandoko:2020:10.1126/scitranslmed.aaw9009,
author = {Prihandoko, R and Kaur, D and Wiegman, CH and Alvarez-Curto, E and Donovan, C and Chachi, L and Ulven, T and Tyas, MR and Euston, E and Dong, Z and Alharbi, AGM and Kim, RY and Lowe, JG and Hansbro, PM and Chung, KF and Brightling, CE and Milligan, G and Tobin, AB},
doi = {10.1126/scitranslmed.aaw9009},
journal = {Science Translational Medicine},
pages = {1--13},
title = {Pathophysiological regulation of lung function by the free fatty acid receptor FFA4},
url = {http://dx.doi.org/10.1126/scitranslmed.aaw9009},
volume = {12},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with inadequate disease control by current frontline treatments means that there is a need to define therapeutic targets for these conditions. Here, we investigate a member of the G protein-coupled receptor family, FFA4, that responds to free circulating fatty acids including dietary omega-3 fatty acids found in fish oils. We show that FFA4, although usually associated with metabolic responses linked with food intake, is expressed in the lung where it is coupled to Gq/11 signaling. Activation of FFA4 by drug-like agonists produced relaxation of murine airway smooth muscle mediated at least in part by the release of the prostaglandin E2 (PGE2) that subsequently acts on EP2 prostanoid receptors. In normal mice, activation of FFA4 resulted in a decrease in lung resistance. In acute and chronic ozone models of pollution-mediated inflammation and house dust mite and cigarette smoke-induced inflammatory disease, FFA4 agonists acted to reduce airway resistance, a response that was absent in mice lacking expression of FFA4. The expression profile of FFA4 in human lung was similar to that observed in mice, and the response to FFA4/FFA1 agonists similarly mediated human airway smooth muscle relaxation ex vivo. Our study provides evidence that pharmacological targeting of lung FFA4, and possibly combined activation of FFA4 and FFA1, has in vivo efficacy and might have therapeutic value in the treatment of bronchoconstriction associated with inflammatory airway diseases such as asthma and COPD.
AU  - Prihandoko,R
AU  - Kaur,D
AU  - Wiegman,CH
AU  - Alvarez-Curto,E
AU  - Donovan,C
AU  - Chachi,L
AU  - Ulven,T
AU  - Tyas,MR
AU  - Euston,E
AU  - Dong,Z
AU  - Alharbi,AGM
AU  - Kim,RY
AU  - Lowe,JG
AU  - Hansbro,PM
AU  - Chung,KF
AU  - Brightling,CE
AU  - Milligan,G
AU  - Tobin,AB
DO  - 10.1126/scitranslmed.aaw9009
EP  - 13
PY  - 2020///
SN  - 1946-6234
SP  - 1
TI  - Pathophysiological regulation of lung function by the free fatty acid receptor FFA4
T2  - Science Translational Medicine
UR  - http://dx.doi.org/10.1126/scitranslmed.aaw9009
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32817367
UR  - https://stm.sciencemag.org/content/12/557/eaaw9009
UR  - http://hdl.handle.net/10044/1/82064
VL  - 12
ER  -
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