ω3 fatty acid metabolite, 12-hydroxyeicosapentaenoic acid, alleviates contact hypersensitivity by downregulation of CXCL1 and CXCL2 gene expression in keratinocytes via retinoid X receptor α

Azusa Saika, Takahiro Nagatake, So ichiro Hirata, Kento Sawane, Jun Adachi, Yuichi Abe, Junko Isoyama, Sakiko Morimoto, Eri Node, Prabha Tiwari, Koji Hosomi, Ayu Matsunaga, Tetsuya Honda, Takeshi Tomonaga, Makoto Arita, Kenji Kabashima, Jun Kunisawa

Research output: Contribution to journalArticlepeer-review

Abstract

ω3 fatty acids show potent bioactivities via conversion into lipid mediators; therefore, metabolism of dietary lipids is a critical determinant in the properties of ω3 fatty acids in the control of allergic inflammatory diseases. However, metabolic progression of ω3 fatty acids in the skin and their roles in the regulation of skin inflammation remains to be clarified. In this study, we found that 12-hydroxyeicosapentaenoic acid (12-HEPE), which is a 12-lipoxygenase metabolite of eicosapentaenoic acid, was the prominent metabolite accumulated in the skin of mice fed ω3 fatty acid-rich linseed oil. Consistently, the gene expression levels of Alox12 and Alox12b, which encode proteins involved in the generation of 12-HEPE, were much higher in the skin than in the other tissues (eg, gut). We also found that the topical application of 12-HEPE inhibited the inflammation associated with contact hypersensitivity by inhibiting neutrophil infiltration into the skin. In human keratinocytes in vitro, 12-HEPE inhibited the expression of two genes encoding neutrophil chemoattractants, CXCL1 and CXCL2, via retinoid X receptor α. Together, the present results demonstrate that the metabolic progression of dietary ω3 fatty acids differs in different organs, and identify 12-HEPE as the dominant ω3 fatty acid metabolite in the skin.

Original languageEnglish
Article numbere21354
JournalFASEB Journal
Volume35
Issue number4
DOIs
Publication statusPublished - 2021 Apr

Keywords

  • 12-hydroxyeicosapentaenoic acid
  • allergic contact dermatitis
  • keratinocytes
  • lipid metabolite
  • retinoid X receptor

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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