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.