15-hydroxyeicosatetraenoic acid (15-HETE)-GPR39 axis: a potential therapeutic target in eosinophilic asthma.
- 1Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, United States.
- 2Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health and Science University, Portland, OR, United States.
Abstract
Arachidonic acid (AA) metabolites play key roles in the pathophysiology of asthma. Along with cyclooxygenase and CYP P450, lipoxygenases (LO) produce these metabolites. 15-hydroxyeicosatetraenoic acid (15-HETE), a product of 15-LO, has been implicated in severe asthma, particularly eosinophilic asthma. This article reviews the AA-15-HETE axis in eosinophilic asthma. 15-HETE contributes to key features of eosinophilic asthma, including eosinophil recruitment, mucus hypersecretion, and airway remodeling. Despite these observations, the downstream signaling mechanisms through which 15-HETE exerts its effects remain incompletely understood. GPR39 has recently been proposed as a potential receptor for 15-HETE, linking lipid metabolism to intracellular signaling involved in inflammation and tissue remodeling. Although the role of GPR39 in asthma has not been studied, its ability to respond to bioactive lipids suggests it may serve as a critical signaling node in eosinophilic inflammation. Taken together, these findings support a model in which the AA-15-HETE-GPR39 axis contributes to the pathogenesis of eosinophilic asthma. Targeting GPR39 may therefore represent a novel and underexplored therapeutic strategy for modulating airway inflammation and remodeling.
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BibTeX
@article{engel202615hydroxyeicosatetraenoic,
title = {{15-hydroxyeicosatetraenoic acid (15-HETE)-GPR39 axis: a potential therapeutic target in eosinophilic asthma.}},
author = {Andrew Engel and Zhenying Nie and Sanjiv Kaul},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1880829},
url = {https://europepmc.org/article/MED/42903481},
note = {CC BY},
}
RIS
TY - JOUR
TI - 15-hydroxyeicosatetraenoic acid (15-HETE)-GPR39 axis: a potential therapeutic target in eosinophilic asthma.
AU - Andrew Engel
AU - Zhenying Nie
AU - Sanjiv Kaul
PY - 2026
DA - 2026/10/06
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1880829
UR - https://europepmc.org/article/MED/42903481
AB - Arachidonic acid (AA) metabolites play key roles in the pathophysiology of asthma. Along with cyclooxygenase and CYP P450, lipoxygenases (LO) produce these metabolites. 15-hydroxyeicosatetraenoic acid (15-HETE), a product of 15-LO, has been implicated in severe asthma, particularly eosinophilic asthma. This article reviews the AA-15-HETE axis in eosinophilic asthma. 15-HETE contributes to key features of eosinophilic asthma, including eosinophil recruitment, mucus hypersecretion, and airway remodeling. Despite these observations, the downstream signaling mechanisms through which 15-HETE exerts its effects remain incompletely understood. GPR39 has recently been proposed as a potential receptor for 15-HETE, linking lipid metabolism to intracellular signaling involved in inflammation and tissue remodeling. Although the role of GPR39 in asthma has not been studied, its ability to respond to bioactive lipids suggests it may serve as a critical signaling node in eosinophilic inflammation. Taken together, these findings support a model in which the AA-15-HETE-GPR39 axis contributes to the pathogenesis of eosinophilic asthma. Targeting GPR39 may therefore represent a novel and underexplored therapeutic strategy for modulating airway inflammation and remodeling.
SN - 1663-9812
ER -