Immunomodulating effects of 13- and 16-hydroxylated docosahexaenoyl ethanolamide in LPS stimulated RAW264.7 macrophages
Autor: | Ian de Bus, Michiel G.J. Balvers, Guido J. E. J. Hooiveld, Sandra J. van Krimpen, Mieke Poland, Bauke Albada, Renger F. Witkamp, Mark V. Boekschoten |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Lipopolysaccharides Docosahexaenoic Acids Macrophage Nitric oxide Immunomodulation Voeding Metabolisme en Genomica 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Docosahexaenoyl ethanolamide Voeding Ethanolamide Animals Immunologic Factors Receptor HNRU&LB Molecular Biology VLAG Nutrition Endocannabinoid biology Chemistry Sirtuin 1 Macrophages Organic Chemistry Cell Biology Organische Chemie Metabolism and Genomics Nutritional Biology Cyclooxygenase 030104 developmental biology RAW 264.7 Cells Biochemistry Docosahexaenoic acid Metabolisme en Genomica TLR4 biology.protein Nutrition Metabolism and Genomics Tumor necrosis factor alpha Transcriptome IRF3 030217 neurology & neurosurgery |
Zdroj: | Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids 1866 (2021) 6 Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids, 1866(6) |
ISSN: | 1879-2618 1388-1981 |
Popis: | Docosahexaenoyl ethanolamide (DHEA), the ethanolamine conjugate of the n-3 long chain polyunsaturated fatty acid docosahexaenoic acid, is endogenously present in the human circulation and in tissues. Its immunomodulating properties have been (partly) attributed to an interaction with the cyclooxygenase-2 (COX-2) enzyme. Recently, we discovered that COX-2 converts DHEA into two oxygenated metabolites, 13- and 16-hydroxylated-DHEA (13- and 16-HDHEA, respectively). It remained unclear whether these oxygenated metabolites also display immunomodulating properties like their parent DHEA. In the current study we investigated the immunomodulating properties of 13- and 16-HDHEA in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The compounds reduced production of tumor necrosis factor alpha (TNFα), interleukin (IL)-1β and IL-1Ra, but did not affect nitric oxide (NO) and IL-6 release. Transcriptome analysis showed that the compounds inhibited the LPS-mediated induction of pro-inflammatory genes (InhbA, Ifit1) and suggested potential inhibition of regulators such as toll-like receptor 4 (TLR4), MyD88, and interferon regulatory factor 3 (IRF3), whereas anti-inflammatory genes (SerpinB2) and potential regulators IL-10, sirtuin 1 (Sirt-1), fluticasone propionate were induced. Additionally, transcriptome analysis of 13-HDHEA suggests a potential anti-angiogenic role. In contrast to the known oxylipin-lowering effects of DHEA, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analyses revealed that 13- and 16-HDHEA did not affect oxylipin formation. Overall, the anti-inflammatory effects of 13-HDHEA and 16-HDHEA are less pronounced compared to their parent molecule DHEA. Therefore, we propose that COX-2 metabolism of DHEA acts as a regulatory mechanism to limit the anti-inflammatory properties of DHEA. |
Databáze: | OpenAIRE |
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