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. Issue 4 (22nd March 2021)

• Record Type: Journal Article
• Authors: Saika, Azusa; Nagatake, Takahiro; Hirata, So‐ichiro; Sawane, Kento; Adachi, Jun; Abe, Yuichi; Isoyama, Junko; Morimoto, Sakiko; Node, Eri; Tiwari, Prabha; Hosomi, Koji; Matsunaga, Ayu; Honda, Tetsuya; Tomonaga, Takeshi; Arita, Makoto; Kabashima, Kenji; Kunisawa, Jun
• Is Part Of: FASEB journal. Volume 35:Issue 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-22
• Subjects: 12‐hydroxyeicosapentaenoic acid -- allergic contact dermatitis -- keratinocytes -- lipid metabolite -- retinoid X receptor; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202001687R
• Languages: English
• ISSNs: 0892-6638

Abstract

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.