The role of 15 lipoxygenase 1 in asthma comes into focus

Joshua A Boyce

doi:10.1172/jci155884

Abstract

IL-4– and IL-13–driven epithelial cell expression of 15 lipoxygenase 1 (15LO1) is a consistent feature of eosinophil-dominated asthma known as type 2–high (T2-high) asthma. The abundant soluble products of arachidonic acid (AA) metabolized by 15LO1 reflect a high level of enzymatic activity in asthma and chronic rhinosinusitis. However, the precise role of 15LO1 and its products in disease pathogenesis remains enigmatic. In this issue of the JCI, Nagasaki and colleagues demonstrate a role for 15LO1 in controlling redox balance and epithelial homeostasis in T2-high asthma by metabolizing AA that is esterified to membrane phospholipids. The findings may pave the way toward the development of 15LO1 inhibitors as asthma treatments.

Highlights

Altered epithelial cell differentiation in chronic respiratory tract inflammation Asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP) are prevalent immune-mediated diseases of the respiratory tract that frequently coexist and cause substantial morbidity [1,2,3]
IL-4Rα in the treatment of severe type 2–high (T2-high) asthma and CRSwNP validates the biological importance of IL-4Rα– inducible products in disease pathophysiology [10, 11], the relative contributions of each remain less clear
Using measures of redox balance in BAL fluids and freshly harvested bronchial epithelial cells from subjects with asthma who were enrolled in two cohort studies, the investigators found higher glutathione disulfide (GSSH) and lower GSH/GSSH ratios in BAL fluids from subjects with severe asthma than those with mild/moderate disease and healthy controls

Summary

Introduction

Altered epithelial cell differentiation in chronic respiratory tract inflammation Asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP) are prevalent immune-mediated diseases of the respiratory tract that frequently coexist and cause substantial morbidity [1,2,3]. ALOX15, encoding 15 lipoxygenase 1 (15LO1), is one of the strongly and consistently expressed IL-4Rα–inducible transcripts by mucosal epithelial cells in T2-high asthma and CRSwNP [7, 9, 12]. While soluble products of 15LO1 activity reflect peroxidation of free PUFAs, oxidative products of esterified PUFAs remain cell associated and are more challenging to study.

Results

Conclusion