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J. Biol. Chem., Vol. 283, Issue 38, 25765-25769, September 19, 2008

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Minireview

Role of Dual Specificity Phosphatases in Biological Responses to Glucocorticoids^*

From the Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom

The powerful anti-inflammatory effects of glucocorticoids (GCs) have been known for more than sixty years, but their molecular mechanisms are still incompletely understood and hotly debated. The GC receptor (GR) was cloned in 1985 and shown to be a transcription factor. Initially, the anti-inflammatory actions of GCs were explained in terms of genes that were up-regulated by the receptor. However, none of these putative mediators seemed able to account for the spectrum of anti-inflammatory responses to GCs. The discovery of a negative regulatory function of GR then shifted the focus away from GC-induced genes as anti-inflammatory mediators. In recent years, attention has begun to move back toward the idea that the anti-inflammatory response to GCs is partially dependent on the positive regulation of gene expression by GR.

^* This minireview will be reprinted in the 2008 Minireview Compendium, which will be available in January, 2009.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1 and additional references.

¹ To whom correspondence should be addressed. E-mail: andy.clark{at}imperial.ac.uk.

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