15-hydroxyeicosatetraenoic acid (15-HETE)-GPR39 axis: a potential therapeutic target in eosinophilic asthma

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.