Dysregulated metabolism of polyunsaturated fatty acids in eosinophilic allergic diseases

Jun Miyata, Koichi Fukunaga, Yusuke Kawashima, Osamu Ohara, Akihiko Kawana, Koichiro Asano, Makoto Arita

Research output: Contribution to journalArticlepeer-review

Abstract

Polyunsaturated fatty acids (PUFAs), represented by the omega-6 fatty acid arachidonic acid (AA) and omega-3 fatty acid docosahexaenoic acid (DHA), are essential components of the human body. PUFAs are converted enzymatically into bioactive lipid mediators, including AA-derived cysteinyl leukotrienes (cys-LTs) and lipoxins and DHA-derived protectins, which orchestrate a wide range of immunological responses. For instance, eosinophils possess the biosynthetic capacity of various lipid mediators through multiple enzymes, including 5-lipoxygenase and 15-lipoxygenase, and play central roles in the regulation of allergic diseases. Dysregulated metabolism of PUFAs is reported, especially in severe asthma, aspirin-exacerbated respiratory disease, and eosinophilic chronic rhinosinusitis (ECRS), which is characterized by the overproduction of cys-LTs and impaired synthesis of pro-resolving mediators. Recently, by performing a multi-omics analysis (lipidomics, proteomics, and transcriptomics), we demonstrated the metabolic derangement of eosinophils in inflamed tissues of patients with ECRS. This abnormality occurred subsequent to altered enzyme expression of gamma-glutamyl transferase-5. In this review, we summarize the previous findings of dysregulated PUFA metabolism in allergic diseases, and discuss future prospective therapeutic strategies for correcting this imbalance.

Original languageEnglish
Article number106477
JournalProstaglandins and Other Lipid Mediators
Volume150
DOIs
Publication statusPublished - 2020 Oct

Keywords

  • 15-lipoxygenase
  • Aspirin-exacerbated respiratory disease
  • Cysteinyl leukotrienes
  • Eosinophilic chronic rhinosinusitis
  • Eosinophils
  • Severe asthma

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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