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Activation of G protein-coupled receptor 40 alleviates STAT6 activation, airway inflammation and mucus hypersecretion in allergic asthma.

Created on 29 Jun 2026

Authors

Chantapol Yimnual, Jenjira Sontikun, Vanason Yaovakhan, Suhaibee Kuno, Phattarin Pothipan, Chatchai Muanprasat, Virawudh Soontornniyomkij, Aekkacha Moonwiriyakit

Published in

Current research in pharmacology and drug discovery. Volume 11. Pages 100260. Epub Jun 16, 2026.

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.

PMID:
42371471
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

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