Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid

• Published in: The Journal of immunology (1950) Vol. 205; no. 10; pp. 2840 - 2849
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 15.11.2020
• Subjects: Animals; Anti-Inflammatory Agents - analysis; Anti-Inflammatory Agents - metabolism; Arachidonic Acid - metabolism; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Cells, Cultured; Fatty Acids, Omega-6 - analysis; Fatty Acids, Omega-6 - metabolism; Fatty Acids, Unsaturated - analysis; Fatty Acids, Unsaturated - metabolism; Humans; Leukotriene B4 - metabolism; Lipidomics; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Transgenic; Neutrophils - immunology; Neutrophils - metabolism; Peritoneal Lavage; Peritonitis - immunology; Peritonitis - pathology; Primary Cell Culture; THP-1 Cells; Zymosan - administration & dosage; Zymosan - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1801653

Polyunsaturated fatty acids (PUFAs) and their metabolites are potent regulators of inflammation. Generally, omega ( )-3 PUFAs are considered proresolving whereas -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 -6 PUFA. Functional studies revealed that AdA potently inhibited the formation of the chemoattractant leukotriene B (LTB ), 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 LTB -dependent murine arthritis model. Our findings are, to our knowledge, the first to indicate that the -6 fatty acid AdA effectively blocks production of LTB by neutrophils and could play a role in resolution of inflammation in vivo.