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)2840-2849
Number of pages10
JournalJournal of Immunology
Volume205
Issue number10
DOIs
StatePublished - Nov 15 2020

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  • Journal Article

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