| Literature DB >> 33008950 |
Hilde Brouwers1, Hulda S Jónasdóttir1,2, Marije E Kuipers2, Joanneke C Kwekkeboom1, Jennifer L Auger3,4, Mayra Gonzalez-Torres3,4, Cristina López-Vicario5, Joan Clària5, Jona Freysdottir6, Ingibjorg Hardardottir6, José Garrido-Mesa7, Lucy V Norling7, Mauro Perretti7, Tom W J Huizinga1, Margreet Kloppenburg1, René E M Toes1, Bryce Binstadt3,4, Martin Giera8, Andreea Ioan-Facsinay1.
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.Entities:
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Year: 2020 PMID： 33008950 DOI： 10.4049/jimmunol.1801653
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422