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 L.
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 - 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 -