Anti-inflammatory and proresolving effects of the omega-6 polyunsaturated fatty acid adrenic acid

Hilde Brouwers, Hulda S. Jonasdottir, Marije E. Kuipers, Joanneke C. Kwekkeboom, Jennifer L. Auger, Mayra Gonzalez-Torres, Cristina Lopez-Vicario, Joan Claria, Jona Freysdottir, Ingibjorg Hardardottir, Jose Garrido-Mesa, Lucy V. Norling, Mauro Perretti, Tom W.J. Huizinga, Margreet Kloppenburg, Rene E.M. Toes, Bryce Binstadt, Martin Giera, Andreea Ioan-Facsinay

Research output: Contribution to journalArticlepeer-review

Abstract

Polyunsaturated fatty acids (PUFAs) and their metabolites are potent regulators of inflammation. Generally, omega (n)-3 PUFAs are considered proresolving whereas n-6 PUFAs are classified as proinflammatory. In this study, we characterized the inflammatory response in murine peritonitis and unexpectedly found the accumulation of adrenic acid (AdA), a poorly studied n-6 PUFA. Functional studies revealed that AdA potently inhibited the formation of the chemoattractant leukotriene B4 (LTB4), specifically in human neutrophils, and this correlated with a reduction of its precursor arachidonic acid (AA) in free form. AdA exposure in human monocyte-derived macrophages enhanced efferocytosis of apoptotic human neutrophils. In vivo, AdA treatment significantly alleviated arthritis in an LTB4-dependent murine arthritis model. Our findings are, to our knowledge, the first to indicate that the n-6 fatty acid AdA effectively blocks production of LTB4 by neutrophils and could play a role in resolution of inflammation in vivo.

Original languageEnglish (US)
Pages (from-to)2873-2882
Number of pages10
JournalJournal of Immunology
Volume205
Issue number10
DOIs
StatePublished - Nov 15 2020

Bibliographical note

Funding Information:
This work was supported by INSERM, Institut Pasteur de Lille, and the Université de Lille. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie Grant Agreement 657107 (to A.V.).

Publisher Copyright:
Copyright © 2020 by The American Association of Immunologists, Inc.

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