dc.contributor.author | PHILPOTT, MP | |
dc.contributor.author | Hannen, R | |
dc.contributor.author | Upton, J | |
dc.date.accessioned | 2017-04-21T15:21:38Z | |
dc.date.available | 2017-04-21T15:21:38Z | |
dc.date.issued | 2017-03-28 | |
dc.date.submitted | 2017-03-28T10:38:40.068Z | |
dc.identifier.citation | Hannen R, Udeh-Momoh C, Upton J, Wright M, Michael A, Gulati A, Rajpopat S, Clayton N, Halsall D, Burrin J, Flower R, Sevilla L, Latorre V, Frame J, Lightman S, Perez P, Philpott M, Dysfunctional Skin-Derived Glucocorticoid Synthesis Is a Pathogenic Mechanism of Psoriasis, The Journal of Investigative Dermatology (2017), doi: 10.1016/j.jid.2017.02.984. | en_US |
dc.identifier.issn | 1523-1747 | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/22560 | |
dc.description.abstract | Glucocorticoids (GC) are the primary steroids that regulate inflammation and have been
exploited therapeutically in inflammatory skin diseases. Despite the broad-spectrum therapeutic
use of GC the biochemical rationale for locally treating inflammatory skin conditions is poorly
understood, as systemic GC production remains largely functional in these patients. GC synthesis
has been well characterised in healthy skin but the pathological consequence has not been
examined. Here we show de novo GC synthesis and GR expression is dysfunctional in both nonlesional
and lesional psoriatic skin. Use of GR epidermal knockout (GREKO) mice with
adrenalectomy allowed for the distinction between local (keratinocyte) and systemic GC activity.
Compensation exhibited by adult GREKO mice demonstrated that keratinocyte-derived GC
synthesis protected skin from topical PMA-induced inflammatory assault. Thus localized de
novo GC synthesis in skin is essential for controlling inflammation and loss of the GC pathway
in psoriatic skin represents an additional pathological process in this complex inflammatory skin
disease. | en_US |
dc.description.sponsorship | Non-animal research was supported by Giuliani SpA, animal studies by grant SAF2014-59474-R (MINECO, Spanish Government) and The Journal of Cell Science (travel award). | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.ispartof | Journal of Investigative Dermatology | |
dc.relation.isreplacedby | 123456789/53643 | |
dc.relation.isreplacedby | https://qmro.qmul.ac.uk/handle/123456789/53643 | |
dc.rights | CC-BY-NC-ND | |
dc.title | Dysfunctional Skin-Derived Glucocorticoid Synthesis Is a Novel Pathogenic Mechanism of Psoriasis | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2017 Elsevier | |
dc.identifier.doi | 10.1016/j.jid.2017.02.984 | |
pubs.publication-status | Accepted | |