Activation of G protein-coupled receptor 40 alleviates STAT6 activation, airway inflammation and mucus hypersecretion in allergic asthma
Issued Date
2026-01-01
Resource Type
eISSN
25902571
Scopus ID
2-s2.0-105041952613
Journal Title
Current Research in Pharmacology and Drug Discovery
Volume
11
Rights Holder(s)
SCOPUS
Bibliographic Citation
Current Research in Pharmacology and Drug Discovery Vol.11 (2026)
Suggested Citation
Yimnual C., Sontikun J., Yaovakhan V., Kuno S., Pothipan P., Muanprasat C., Soontornniyomkij V., Moonwiriyakit A. Activation of G protein-coupled receptor 40 alleviates STAT6 activation, airway inflammation and mucus hypersecretion in allergic asthma. Current Research in Pharmacology and Drug Discovery Vol.11 (2026). doi:10.1016/j.crphar.2026.100260 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/117443
Title
Activation of G protein-coupled receptor 40 alleviates STAT6 activation, airway inflammation and mucus hypersecretion in allergic asthma
Corresponding Author(s)
Other Contributor(s)
Abstract
G-protein coupled receptor 40 (GPR40), also termed free fatty acid receptor 1 (FFAR1) is a promising molecular target for treating chronic metabolic and inflammatory diseases. Despite the antiasthmatic benefit of GPR40 agonists such as omega-3 polyunsaturated fatty acids, it remains unclear whether GPR40 activation improves allergic asthmatic outcomes. The present study investigated the ameliorative effect of GPR40 activation on IL-13-induced allergic inflammation in human bronchial epithelial 16HBE14o-cells and in the ovalbumin-induced asthmatic murine model. The increasing concentration of GPR40 agonists GW9508 and TAK875, markedly mitigated IL-13–induced STAT6 phosphorylation and MUC5AC hypersecretion, suggesting mitigated type 2 inflammation in 16HBE14o-cells. The selective GPR40 antagonists DC260126 and GW1100 both strikingly abolished the anti-inflammatory effect of GW9508. In the asthmatic mouse model, intraperitoneal administration of GW9508 (10 mg/kg) alleviated ovalbumin-induced mucus hypersecretion and airway inflammation, with a reduction in STAT6 phosphorylation in lung tissue. Our findings suggest that GPR40 activation represents a novel therapeutic strategy for STAT6-mediated or type-2-inflammation mediated diseases such as allergic asthma.