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Pro-Resolving Mediators promote resolution in a human skin model of UV-killed Escherichia coli-driven acute inflammation

Motwani, M; Colas, R; George, M; Flint, J; Dalli, J; Richard-Loendt, A; De Maeyer, RPH; ... Gilroy, D; + view all (2018) Pro-Resolving Mediators promote resolution in a human skin model of UV-killed Escherichia coli-driven acute inflammation. Journal of Clinical Investigation , 3 (6) , Article e94463. 10.1172/jci.insight.94463. Green open access

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Abstract

While the treatment of inflammatory disorders is generally based on inhibiting factors that drive onset of inflammation, these therapies can compromise healing (NSAIDs) or dampen immunity against infections (biologics). In search of new antiinflammatories, efforts have focused on harnessing endogenous pathways that drive resolution of inflammation for therapeutic gain. Identification of specialized pro-resolving mediators (SPMs) (lipoxins, resolvins, protectins, maresins) as effector molecules of resolution has shown promise in this regard. However, their action on inflammatory resolution in humans is unknown. Here, we demonstrate using a model of UV-killed Escherichia coli–triggered skin inflammation that SPMs are biosynthesized at the local site at the start of resolution, coinciding with the expression of receptors that transduce their actions. These include receptors for lipoxin A4 (ALX/FPR2), resolvin E1 (ChemR23), resolvin D2 (GPR18), and resolvin D1 (GPR32) that were differentially expressed on the endothelium and infiltrating leukocytes. Administering SPMs into the inflamed site 4 hours after bacterial injection caused a reduction in PMN numbers over the ensuing 6 hours, the phase of active resolution in this model. These results indicate that in humans, the appearance of SPMs and their receptors is associated with the beginning of inflammatory resolution and that their therapeutic supplementation enhanced the resolution response.

Type: Article
Title: Pro-Resolving Mediators promote resolution in a human skin model of UV-killed Escherichia coli-driven acute inflammation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/jci.insight.94463
Publisher version: https://doi.org/10.1172/jci.insight.94463
Language: English
Additional information: License: This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
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 Population Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/10044010
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