Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

Christopher Burnsides,1,* Jacqueline Corry,1,* Jacob Alexander,1 Catherine Balint,1 David Cosmar,1 Gary Phillips,2 Jeanette I Webster Marketon1,31Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Center for Biostatistics, 3Institute for Behavioral Me...

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Autores principales:	Burnsides C, Corry J, Alexander J, Balint C, Cosmar D, Phillips G, Webster Marketon JI
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/01148332773a462ca3cb622135703d1f
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spelling	oai:doaj.org-article:01148332773a462ca3cb622135703d1f2021-12-02T05:56:57ZEx vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity1178-7031https://doaj.org/article/01148332773a462ca3cb622135703d1f2012-08-01T00:00:00Zhttp://www.dovepress.com/ex-vivo-stimulation-of-whole-blood-as-a-means-to-determine-glucocortic-a10783https://doaj.org/toc/1178-7031Christopher Burnsides,1,* Jacqueline Corry,1,* Jacob Alexander,1 Catherine Balint,1 David Cosmar,1 Gary Phillips,2 Jeanette I Webster Marketon1,31Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Center for Biostatistics, 3Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, Columbus, OH, USA*JC and CB have equally contributed to this workPurpose: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity.Patients and methods: Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR) up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay.Results: We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNF&alpha;) are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC50 and IC50 concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day.Conclusion: In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.Keywords: glucocorticoid responsiveness, gene regulation, nuclear receptor, GILZ, FKBP51, cytokinesBurnsides CCorry JAlexander JBalint CCosmar DPhillips GWebster Marketon JIDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2012, Iss default, Pp 89-97 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Burnsides C Corry J Alexander J Balint C Cosmar D Phillips G Webster Marketon JI Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
description	Christopher Burnsides,1,* Jacqueline Corry,1,* Jacob Alexander,1 Catherine Balint,1 David Cosmar,1 Gary Phillips,2 Jeanette I Webster Marketon1,31Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Center for Biostatistics, 3Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, Columbus, OH, USA*JC and CB have equally contributed to this workPurpose: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity.Patients and methods: Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR) up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay.Results: We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNF&alpha;) are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC50 and IC50 concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day.Conclusion: In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.Keywords: glucocorticoid responsiveness, gene regulation, nuclear receptor, GILZ, FKBP51, cytokines
format	article
author	Burnsides C Corry J Alexander J Balint C Cosmar D Phillips G Webster Marketon JI
author_facet	Burnsides C Corry J Alexander J Balint C Cosmar D Phillips G Webster Marketon JI
author_sort	Burnsides C
title	Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
title_short	Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
title_full	Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
title_fullStr	Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
title_full_unstemmed	Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
title_sort	ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/01148332773a462ca3cb622135703d1f
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Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

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