Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process

In order to find an explanation for corticosteroid resistance we assessed whether inhibition by dexamethasone (DEX) of the stimulated production of TNF-∝, IL-6, PGE2 and LTB4 by peripheral blood mononuclear cells (MNC) depends on binding to the glucocorticoid receptor (GR), and whether it is determi...

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Main Authors: G. S. Madretsma, A. P. M. van Dijk, C. J. A. M. Tak, J. H. P. Wilson, F. J. Zijlstra
Format: Article
Language:English
Published: Hindawi Limited 1996-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/S0962935196000166
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spelling doaj-8054adf4640a465b862f59d8aa883eb32020-11-24T23:29:53ZengHindawi LimitedMediators of Inflammation0962-93511466-18611996-01-015210010310.1155/S0962935196000166Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated processG. S. Madretsma0A. P. M. van Dijk1C. J. A. M. Tak2J. H. P. Wilson3F. J. Zijlstra4Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The NetherlandsDepartment of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The NetherlandsDepartment of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The NetherlandsDepartment of Internal Medicine II, University Hospital Dijkzigt, Rotterdam, The NetherlandsDepartment of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The NetherlandsIn order to find an explanation for corticosteroid resistance we assessed whether inhibition by dexamethasone (DEX) of the stimulated production of TNF-∝, IL-6, PGE2 and LTB4 by peripheral blood mononuclear cells (MNC) depends on binding to the glucocorticoid receptor (GR), and whether it is determined by the number or the affinity of the GR of these cells. GR number and affinity of MNC were determined by means of a whole cell DEX binding assay. MNC were incubated with DEX and LPS or A23187 in the absence or presence of RU486, a potent steroid antagonist. DEX caused a concentration dependent inhibition of TNF-∝, IL-6 and PGE2 production but had no effect on LTB4 production. RU486 significantly blocked the effect of DEX, but no correlations were found between the inhibition of mediator release and the Kd or receptor number.http://dx.doi.org/10.1155/S0962935196000166
collection DOAJ
language English
format Article
sources DOAJ
author G. S. Madretsma
A. P. M. van Dijk
C. J. A. M. Tak
J. H. P. Wilson
F. J. Zijlstra
spellingShingle G. S. Madretsma
A. P. M. van Dijk
C. J. A. M. Tak
J. H. P. Wilson
F. J. Zijlstra
Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
Mediators of Inflammation
author_facet G. S. Madretsma
A. P. M. van Dijk
C. J. A. M. Tak
J. H. P. Wilson
F. J. Zijlstra
author_sort G. S. Madretsma
title Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
title_short Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
title_full Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
title_fullStr Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
title_full_unstemmed Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
title_sort inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process
publisher Hindawi Limited
series Mediators of Inflammation
issn 0962-9351
1466-1861
publishDate 1996-01-01
description In order to find an explanation for corticosteroid resistance we assessed whether inhibition by dexamethasone (DEX) of the stimulated production of TNF-∝, IL-6, PGE2 and LTB4 by peripheral blood mononuclear cells (MNC) depends on binding to the glucocorticoid receptor (GR), and whether it is determined by the number or the affinity of the GR of these cells. GR number and affinity of MNC were determined by means of a whole cell DEX binding assay. MNC were incubated with DEX and LPS or A23187 in the absence or presence of RU486, a potent steroid antagonist. DEX caused a concentration dependent inhibition of TNF-∝, IL-6 and PGE2 production but had no effect on LTB4 production. RU486 significantly blocked the effect of DEX, but no correlations were found between the inhibition of mediator release and the Kd or receptor number.
url http://dx.doi.org/10.1155/S0962935196000166
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