J Clin Invest. 2022 Jan 4;132(1). doi: 10.1172/JCI155884.
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.
IL-4- 和 IL-13 驱动的上皮细胞 15 脂氧合酶 1（15LO1）的表达是嗜酸性粒细胞占主导的哮喘（称为 2 型高（T2-高）哮喘）的一个一致特征。15LO1 代谢花生四烯酸（AA）产生的丰富可溶性产物反映了哮喘和慢性鼻-鼻窦炎中酶活性的高水平。然而，15LO1 及其产物在疾病发病机制中的确切作用仍然是个谜。在本期 JCI 中，Nagasaki 及其同事通过代谢酯化到膜磷脂的 AA 证明 15LO1 在控制 T2-高哮喘中的氧化还原平衡和上皮细胞稳态方面发挥作用。这些发现可能为开发 15LO1 抑制剂作为哮喘治疗方法铺平道路。
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