Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid
Hilde Brouwers, Hulda S. Jónasdóttir, Marije E. Kuipers, Joanneke C. Kwekkeboom, Jennifer L. Auger, Mayra I. Gonzalez-Torres, Cristina López‐Vicario, Joan Clària, Jóna Freysdóttir, Ingibjörg Harðardóttir, José Garrido‐Mesa, Lucy V. Norling, Mauro Perretti, T. Huizinga, M. Kloppenburg, René E. M. Toes, Bryce A. Binstadt, Martin Giera, Andreea Ioan‐Facsinay
Abstract
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.