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Mucosal Immunol. 2020 Jan 6. doi: 10.1038/s41385-019-0245-2. [Epub ahead of print]

A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA.

Author information

1
Department of Food Technology, University of Applied Sciences Fulda, Fulda, Germany. daniela.fussbroich@lt.hs-fulda.de.
2
Division for Allergy, Pneumology and Cystic Fibrosis, Department for Children and Adolescence, Goethe-University, Frankfurt/Main, Germany. daniela.fussbroich@lt.hs-fulda.de.
3
Faculty of Biological Sciences, Goethe University Frankfurt/Main, Frankfurt/Main, Germany. daniela.fussbroich@lt.hs-fulda.de.
4
Lipid Mediator Unit, William Harvey Research Institute, Bart's and the London School of Medicine, Queen Mary University of London, London, UK.
5
Division for Allergy, Pneumology and Cystic Fibrosis, Department for Children and Adolescence, Goethe-University, Frankfurt/Main, Germany.
6
Department of Food Technology, University of Applied Sciences Fulda, Fulda, Germany.
7
Department of Trauma, Hand & Reconstructive Surgery, Goethe-University, Frankfurt/Main, Germany.
8
Division of Nephrology, Department of Internal Medicine III, Goethe-University, Frankfurt/Main, Germany.
9
Centre for inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK.

Abstract

Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-γ, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB5 and LTC5 and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB5 contributes to granulocytes' migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.

PMID:
31907365
DOI:
10.1038/s41385-019-0245-2

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