The omega-3 postbiotic trans-10-cis-15-octadecadienoic acid attenuates contact hypersensitivity in mice through downregulation of vascular endothelial growth factor A

Autor: Azusa Saika, Takahiro Nagatake, Shigenobu Kishino, Nahoko Kitamura, Tetsuya Honda, Koji Hosomi, Prabha Tiwari, Eri Node, Soichiro Kawai, Saki Kondo, Kei Ishida, Kenji Kabashima, Jun Ogawa, Jun Kunisawa
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Cellular and Infection Microbiology, Vol 14 (2024)
Druh dokumentu: article
ISSN: 2235-2988
DOI: 10.3389/fcimb.2024.1355679
Popis: Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid–derived metabolites: trans-10-cis-15-octadecadienoic acid (t10,c15-18:2) and cis-9-cis-15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2—but not c9,c15-18:2—attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid–derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis–induced inflammation.
Databáze: Directory of Open Access Journals