Anti-inflammatory and proresolving effects of the omega-6 polyunsaturated fatty acid adrenic acid

Brouwers, H.; Jonasdottir, H.S.; Kuipers, M.E.; Kwekkeboom, J.C.; Auger, J.L.; Gonzalez-Torres, M.; ... ; Ioan-Facsinay, A. (2020)

Article / Letter to editor

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 B-4 (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.

• All authors: Brouwers, H.; Jonasdottir, H.S.; Kuipers, M.E.; Kwekkeboom, J.C.; Auger, J.L.; Gonzalez-Torres, M.; Lopez-Vicario, C.; Claria, J.; Freysdottir, J.; Hardardottir, I.; Garrido-Mesa, J.; Norling, L.V.; Perretti, M.; Huizinga, T.W.J.; Kloppenburg, M.; Toes, R.E.M.; Binstadt, B.; Giera, M.; Ioan-Facsinay, A.
• Date: 2020-11-15
• Journal: Journal of Immunology
• Volume: 205
• Issue: 10
• Pages: 2840 - 2849
• DOI: doi:10.4049/jimmunol.1801653
• Link: https://journals.aai.org/jimmunol/article/205/10/2840/107801/Anti-Inflam...