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.
Animals
Antibodies, Monoclonal
/ drug effects
Bone Marrow Cells
Chemokine CXCL1
/ genetics
Dermatitis, Contact
/ prevention & control
Diet
Dinitrofluorobenzene
Down-Regulation
Eicosapentaenoic Acid
/ analogs & derivatives
Female
Gene Expression Regulation
/ drug effects
HaCaT Cells
Humans
Keratinocytes
/ drug effects
Linseed Oil
/ administration & dosage
Mice
12-hydroxyeicosapentaenoic acid
allergic contact dermatitis
keratinocytes
lipid metabolite
retinoid X receptor
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
14
12
2020
received:
09
07
2020
accepted:
23
12
2020
entrez:
22
3
2021
pubmed:
23
3
2021
medline:
22
7
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33749892
doi: 10.1096/fj.202001687R
doi:
Substances chimiques
Antibodies, Monoclonal
0
Chemokine CXCL1
0
12-hydroxy-5,8,10,14,17-eicospentaenoic acid
74838-73-6
Linseed Oil
8001-26-1
Eicosapentaenoic Acid
AAN7QOV9EA
techneticum TC-99M fanolesomab
AMF7KOE318
Dinitrofluorobenzene
D241E059U6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21354Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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