Journal of immunology (Baltimore, Md. : 1950) · 2020
Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid.
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Brouwers Hilde, Jónasdóttir Hulda S, Kuipers Marije E, Kwekkeboom Joanneke C, Auger Jennifer L, Gonzalez-Torres Mayra, López-Vicario Cristina, Clària Joan, Freysdottir Jona, Hardardottir Ingibjorg, Garrido-Mesa José, Norling Lucy V, Perretti Mauro, Huizinga Tom W J, Kloppenburg Margreet, Toes René E M, Binstadt Bryce, Giera Martin, Ioan-Facsinay Andreea
Аннотация
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.