Arachidonic acid 15-lipoxygenase (ALOX15) is an enzyme that can oxidize polyunsaturated fatty acids. ALOX15 is strongly expressed in airway epithelial cells, where it catalyzes the conversion of arachidonic acid to 15-hydroxyeicosatetraenoic acid (15-HETE) involved in various airway inflammatory diseases. Interleukin (IL)-4 and IL-13 induce ALOX15 expression by activating Jak2 and Tyk2 kinases as well as signal transducers and activators of transcription (STATs) 1/3/5/6. ALOX15 up-regulation and subsequent association with phosphatidylethanolamine-binding protein 1 (PEBP1) activate the mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway, thus inducing eosinophil-mediated airway inflammation. In addition, ALOX15 plays a significant role in promoting the migration of immune cells, such as immature dendritic cells, activated T cells, and mast cells, and airway remodeling, including goblet cell differentiation. Genome-wide association studies have revealed multiple ALOX15 variants and their significant correlation with the risk of developing airway diseases. The epigenetic modifications of the ALOX15 gene, such as DNA methylation and histone modifications, have been shown to closely relate with airway inflammation. This review summarizes the role of ALOX15 in different phenotypes of asthma, chronic obstructive pulmonary disease, chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and nasal polyps, suggesting new treatment strategies for these airway inflammatory diseases with complex etiology and poor treatment response.
基金：
national key R&D program of China [2016YFC20160905200]; program for the Changjiang scholars and innovative research teamProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT13082]; national natural science foundation of ChinaNational Natural Science Foundation of China (NSFC) [81630023, 81970849, 82071022]; Beijing municipal science and technology project [Z181100001618002]; CAMS Innovation Fund for Medical Sciences [2019-I2M-5-022]; Beijing Municipal Administration of Hospitals' Mission Plan [SML20150203]; Beijing health bureau program for high level talents [2014-3-018]; Cross-disciplinary Collaborative Program of Beijing Nova Program [xxjc201712]; public welfare development and reform pilot project [2019-10]
第一作者机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, 17 HouGouHuTong, Beijing 100005, Peoples R China[3]Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, Beijing, Peoples R China[*1]Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, No. 17, HouGouHuTong, DongCheng District, Beijing 100005, P.R. China.[*2]Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, No. 17, HouGouHuTong, DongCheng District, Beijing 100005, P.R. China.
推荐引用方式(GB/T 7714)：
Xu Xu,Li Jingyun,Zhang Yuan,et al.Arachidonic Acid 15-Lipoxygenase: Effects of Its Expression, Metabolites, and Genetic and Epigenetic Variations on Airway Inflammation[J].ALLERGY ASTHMA & IMMUNOLOGY RESEARCH.2021,13(5):684-696.doi:10.4168/aair.2021.13.5.684.
APA：
Xu, Xu,Li, Jingyun,Zhang, Yuan&Zhang, Luo.(2021).Arachidonic Acid 15-Lipoxygenase: Effects of Its Expression, Metabolites, and Genetic and Epigenetic Variations on Airway Inflammation.ALLERGY ASTHMA & IMMUNOLOGY RESEARCH,13,(5)
MLA：
Xu, Xu,et al."Arachidonic Acid 15-Lipoxygenase: Effects of Its Expression, Metabolites, and Genetic and Epigenetic Variations on Airway Inflammation".ALLERGY ASTHMA & IMMUNOLOGY RESEARCH 13..5(2021):684-696
