UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

CYP450-derived oxylipins mediate inflammatory resolution

Gilroy, DW; Edin, ML; De Maeyer, RP; Bystrom, J; Newson, J; Lih, FB; Stables, M; ... Bishop-Bailey, D; + view all (2016) CYP450-derived oxylipins mediate inflammatory resolution. Proceedings of the National Academy of Sciences of the United States of America , 113 (23) E3240-E3249. 10.1073/pnas.1521453113. Green open access

[img]
Preview
Text
Gilroy et al CYP450-derived oxylipins mediate inflammatory resolution AAM.pdf

Download (541kB) | Preview

Abstract

Resolution of inflammation has emerged as an active process in immunobiology, with cells of the mononuclear phagocyte system being critical in mediating efferocytosis and wound debridement and bridging the gap between innate and adaptive immunity. Here we investigated the roles of cytochrome P450 (CYP)-derived epoxy-oxylipins in a well-characterized model of sterile resolving peritonitis in the mouse. Epoxy-oxylipins were produced in a biphasic manner during the peaks of acute (4 h) and resolution phases (24-48 h) of the response. The epoxygenase inhibitor SKF525A (epoxI) given at 24 h selectively inhibited arachidonic acid- and linoleic acid-derived CYP450-epoxy-oxlipins and resulted in a dramatic influx in monocytes. The epoxI-recruited monocytes were strongly GR1(+), Ly6c(hi), CCR2(hi), CCL2(hi), and CX3CR1(lo) In addition, expression of F4/80 and the recruitment of T cells, B cells, and dendritic cells were suppressed. sEH (Ephx2)(-/-) mice, which have elevated epoxy-oxylipins, demonstrated opposing effects to epoxI-treated mice: reduced Ly6c(hi) monocytes and elevated F4/80(hi) macrophages and B, T, and dendritic cells. Ly6c(hi) and Ly6c(lo) monocytes, resident macrophages, and recruited dendritic cells all showed a dramatic change in their resolution signature following in vivo epoxI treatment. Markers of macrophage differentiation CD11b, MerTK, and CD103 were reduced, and monocyte-derived macrophages and resident macrophages ex vivo showed greatly impaired phagocytosis of zymosan and efferocytosis of apoptotic thymocytes following epoxI treatment. These findings demonstrate that epoxy-oxylipins have a critical role in monocyte lineage recruitment and activity to promote inflammatory resolution and represent a previously unidentified internal regulatory system governing the establishment of adaptive immunity.

Type: Article
Title: CYP450-derived oxylipins mediate inflammatory resolution
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1521453113
Publisher version: http://dx.doi.org/10.1073/pnas.1521453113
Language: English
Additional information: Copyright © 2016 National Academy of Sciences. The published version of record is available on the journal's website at http://dx.doi.org/10.1073/pnas.1521453113
Keywords: epoxygenase, monocyte, oxylipins, phagocytosis, resolution
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1493150
Downloads since deposit
58Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item