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Updated: Aug 31, 2026
Immunofluorescent Labeling in Nasal Mucosa Tissue Sections of Allergic Rhinitis Rats via Multicolor Immunoassay
Published on: September 22, 2023
ALOX15-driven ω-6 fatty acid metabolism promotes type 2 inflammation in eosinophilic chronic rhinosinusitis with
Masafumi Sakashita1,2, Masanori Kidoguchi1, Yoshimasa Imoto1
1Division of Otorhinolaryngology-Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Background:
Local lipid metabolism contributes to immune homeostasis in the nasal mucosa and the pathogenesis of chronic rhinosinusitis. However, lipid mediator networks underlying eosinophilic chronic rhinosinusitis (ECRS) remain poorly defined.
Objective:
To characterize fatty acid-derived lipid mediator profiles in nasal polyps (NPs) from patients with and without ECRS and identify pathways associated with eosinophilic inflammation.
Methods:
Lipidomic profiling was performed using LC-MS/MS on NP tissues from patients with ECRS (n = 4) and without ECRS (n = 4). A total of 158 ω-6 and ω-3 fatty acid-derived lipid mediators were quantified. Arachidonate 15-lipoxygenase (ALOX15) pathway activity was evaluated by quantitative PCR and ELISA.
Results:
ECRS NPs displayed a distinct lipidomic signature compared with non-ECRS NPs. ECRS NPs exhibited increased levels of proinflammatory ω-6 fatty acid metabolites, including 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid, along with elevated ALOX15 pathway products and higher ALOX15 mRNA expression. Anti-inflammatory specialized proresolving mediators, such as lipoxin A4, were also elevated within the ω-6 pathway, and lipoxin A4 levels correlated with 15-HETE levels. These patterns indicate the concurrent activation of pro- and anti-inflammatory pathways, with a predominance of ALOX15-driven ω-6 metabolites in ECRS. In contrast, the ω-3 fatty acid pathway showed only modest increases in 14,15-DiHETE and resolvin D2, suggesting a limited compensatory resolution response compared with the robust ALOX15-dependent ω-6 activity.
Conclusions:
ECRS NPs exhibit a skewed lipid mediator profile characterized by enhanced ALOX15-dependent ω-6 metabolism and insufficient resolution activity. This imbalance may underlie persistent type 2 inflammation in ECRS and suggests that targeting the 15-lipoxygenase pathway may offer therapeutic benefits.
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