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Glucocorticoid receptors: finding the middle ground
Sofie J. Desmet, Karolien De Bosscher
Sofie J. Desmet, Karolien De Bosscher
Published March 20, 2017
Citation Information: J Clin Invest. 2017;127(4):1136-1145. https://doi.org/10.1172/JCI88886.
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Review Series

Glucocorticoid receptors: finding the middle ground

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Abstract

Glucocorticoids (GCs; referred to clinically as corticosteroids) are steroid hormones with potent anti-inflammatory and immune modulatory profiles. Depending on the context, these hormones can also mediate pro-inflammatory activities, thereby serving as primers of the immune system. Their target receptor, the GC receptor (GR), is a multi-tasking transcription factor, changing its role and function depending on cellular and organismal needs. To get a clearer idea of how to improve the safety profile of GCs, recent studies have investigated the complex mechanisms underlying GR functions. One of the key findings includes both pro- and anti-inflammatory roles of GR, and a future challenge will be to understand how such paradoxical findings can be reconciled and how GR ultimately shifts the balance to a net anti-inflammatory profile. As such, there is consensus that GR deserves a second life as a drug target, with either refined classic GCs or a novel generation of nonsteroidal GR-targeting molecules, to meet the increasing clinical needs of today to treat inflammation and cancer.

Authors

Sofie J. Desmet, Karolien De Bosscher

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Figure 2

GCs act at multiple levels in the inflammatory pathway.

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GCs act at multiple levels in the inflammatory pathway.
An inflamed cell...
An inflamed cell is depicted, along with inflammatory mediators (red), which show a signal transduction pathway leading to the activation of NF-κB and AP-1, which subsequently drive proinflammatory gene expression. GC-mediated and GR-triggered responses are depicted (green), including feedback and feedforward mediators, as described in the text. This includes upregulation and activities of various proteins, e.g., MKP-1, ZFP36, IRAK-M, and SphK1. IKK, IκBα kinase; IRAK, IL-1R–associated kinase-4; S1P, sphingosine-1-phosphate.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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