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Anti-inflammatory Effect of Polyunsaturated Fatty Acid N-Acylethanolamines Mediated by Macrophage Activity In Vitro and In Vivo

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Abstract

In recent years, there has been increasing interest in studying the anti-inflammatory activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines, NAE), which are highly active lipid mediators. The results of this study demonstrate that a dietary supplement (DS) of fatty acid-derived NAEs reduces LPS-induced inflammation. The processes of cell proliferation, as well as the dynamics of Iba-1-, CD68-, and CD163-positive macrophage activity within the thymus and spleen were studied. The production of pro-inflammatory cytokines (TNF, IL1β, IL6, and INFγ), ROS, NO, and nitrites was evaluated in the blood serum, thymus, and LPS-stimulated RAW264.7 mouse macrophages. In vitro and in vivo experiments have shown that DS (1) prevents LPS-induced changes in the morphological structure of the thymus and spleen; (2) levels out changes in cell proliferation; (3) inhibits the activity of Iba-1 and CD68-positive cells; (4) reduces the production of pro-inflammatory cytokines (TNF, IL1β, IL6, and INFγ), ROS, and CD68; and (5) enhances the activity of CD-163-positive cells. In general, the results of this study demonstrate the complex effect of DS on inflammatory processes in the central and peripheral immune systems.

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Data Availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Funding

This research was funded by the Ministry of Science and Higher Education, Russian Federation (grant 13.1902.21.0012; contract no. 075–15-2020–796).

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  1. A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041, Vladivostok, Russia

    Anastasia Egoraeva, Anna Tyrtyshnaia, Arina Ponomarenko, Darya Ivashkevich, Ruslan Sultanov & Igor Manzhulo

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Contributions

Conceptualization: A.E., A.T., and I.M.; methodology: A.T., A.E., I.M., A.P., R.S., and D.I.; validation: A.E. and I.M.; formal analysis: A.E., A.T., and I.M.; investigation: A.T., A.E., I.M., A.P., R.S., and D.I.; resources: A.T., I.M., and R.S.; data curation: I.M.; writing—original draft preparation: A.E., I.M., and A.P.; writing—review and editing: A.E., A.T., and I.M.; visualization: I.M.; supervision: A.T. and I.M.; project administration: A.E. and I.M.; funding acquisition: I.M. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Igor Manzhulo.

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All experimental procedures were approved by the Animal Ethics Committee at the A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences (no. 1.3/2022) according to the Laboratory Animal Welfare guidelines and the European Communities Council Directive 2010/63/EU.

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Egoraeva, A., Tyrtyshnaia, A., Ponomarenko, A. et al. Anti-inflammatory Effect of Polyunsaturated Fatty Acid N-Acylethanolamines Mediated by Macrophage Activity In Vitro and In Vivo. Inflammation 46, 2306–2319 (2023). https://doi.org/10.1007/s10753-023-01879-2

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