TY - JOUR
T1 - Anti-inflammatory and proresolving effects of the omega-6 polyunsaturated fatty acid adrenic acid
AU - Brouwers, Hilde
AU - Jonasdottir, Hulda S.
AU - Kuipers, Marije E.
AU - Kwekkeboom, Joanneke C.
AU - Auger, Jennifer
AU - Gonzalez-Torres, Mayra
AU - Lopez-Vicario, Cristina
AU - Claria, Joan
AU - Freysdottir, Jona
AU - Hardardottir, Ingibjorg
AU - Garrido-Mesa, Jose
AU - Norling, Lucy V.
AU - Perretti, Mauro
AU - Huizinga, Tom W.J.
AU - Kloppenburg, Margreet
AU - Toes, Rene E.M.
AU - Binstadt, Bryce
AU - Giera, Martin
AU - Ioan-Facsinay, Andreea
N1 - Funding Information:
This work was supported by INSERM, Institut Pasteur de Lille, and the Université de Lille. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie Grant Agreement 657107 (to A.V.).
Publisher Copyright:
Copyright © 2020 by The American Association of Immunologists, Inc.
PY - 2020/11/15
Y1 - 2020/11/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1801653
DO - 10.4049/jimmunol.1801653
M3 - Article
C2 - 33008950
AN - SCOPUS:85095976592
SN - 0022-1767
VL - 205
SP - 2840
EP - 2849
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -