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Open Access Highly Accessed Research article

Dexamethasone restrains ongoing expression of interleukin-23p19 in peripheral blood-derived human macrophages

Linda Palma*, Carla Sfara, Antonella Antonelli and Mauro Magnani

Author Affiliations

Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Via A. Saffi, 2, 61029 Urbino, PU, Italy

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BMC Pharmacology 2011, 11:8  doi:10.1186/1471-2210-11-8

Published: 26 July 2011

Abstract

Background

Since its recent discovery, interleukin-23 has been shown to be involved in the pathogenesis of autoimmune diseases favoring the development of a T cell subset referred to as T helper 17. Glucocorticoids are widely employed in inflammatory and autoimmune diseases as they inhibit pro-inflammatory signaling and prevent production of inflammation mediators. Very limited information is available about the efficacy of synthetic glucocorticoids in containing the expression of interleukin-23 under cell activation.

Results

We demonstrate here that the glucocorticoid analogue dexamethasone administered to human monocyte-derived macrophages is indeed able to restrain the expression of interleukin-23 once it has been triggered by a pro-inflammatory stimulus. This effect of dexamethasone is here demonstrated being secondary to suppression of p38 MAPK activity, and involving a protein phosphatase - likely MAPK phosphatase-1 (MKP-1).

Conclusions

Results reported in this paper show that a 10 nanomolar dose of dexamethasone not only prevents inflammatory activation but is also efficacious in confining active inflammation. This effect is here demonstrated not to occur through "canonical" inhibition of the NF-κB transcription factor but through a distinct cascade of down-modulation, that underlines the importance of the transactivating activity of glucocorticoid receptor in the context of its anti-inflammatory action.