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Published in: Journal of Clinical Immunology 1/2011

01-02-2011

Dexamethasone-Induced FKBP51 Expression in Peripheral Blood Mononuclear Cells Could Play a Role in Predicting the Response of Asthmatics to Treatment with Corticosteroids

Authors: Eunyoung Chun, Hyun-Seung Lee, Bo-Ram Bang, Tae-Wan Kim, So-Hee Lee, Ju-Han Kim, Sang-Heon Cho, Kyung-Up Min, You-Young Kim, Heung-Woo Park

Published in: Journal of Clinical Immunology | Issue 1/2011

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Abstract

Background

Corticosteroids (CSs) are the preferred anti-inflammatory therapy for the treatment of asthma, but the responses of asthmatics to CSs are known to vary. It has thus become important to discover reliable markers in predicting responses to CSs.

Methods

We performed time-series microarrays using a murine model of asthma after a single dose of dexamethasone, based on the assumption that the gene showing a greater change in response to CSs can also be a potential marker for that finding. We then evaluated the clinical meaning of the gene discovered in the microarray experiments.

Results

We found that the expression of FK506 binding protein 51 gene (FKBP51) in lung tissue markedly increased after dexamethasone treatment in a murine model of asthma. We then measured dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells (PBMCs) in asthmatics. Dexamethasone-induced FKBP51 expression in PBMCs was significantly higher in severe asthmatics compared with mild-to-moderate asthmatics treated with inhaled CSs. In addition, we found that dexamethasone-induced FKBP51 expression in PBMCs was inversely correlated with improvement in lung function after treatment with orally administered prednisolone in six steroid-naive asthmatics.

Conclusion

Dexamethasone-induced FKBP51 expression in PBMCs may be a reliable and practical biomarker in predicting the response to CSs in asthmatics.
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Literature
1.
go back to reference National Asthma Education and Prevention Program (2007) Guidelines for the diagnosis and management of asthma: Expert Panel Report 2. Publication #08-4051. Bethesda (MD): National Institutes of Health/National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program (2007) Guidelines for the diagnosis and management of asthma: Expert Panel Report 2. Publication #08-4051. Bethesda (MD): National Institutes of Health/National Heart, Lung, and Blood Institute
2.
go back to reference Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31:143–78.CrossRefPubMed Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31:143–78.CrossRefPubMed
3.
go back to reference Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999;130:487–95.PubMed Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999;130:487–95.PubMed
4.
go back to reference Kerrebijn KF, van Essen-Zandvliet EE, Neijens HJ. Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma. J Allergy Clin Immunol. 1987;79:653–9.CrossRefPubMed Kerrebijn KF, van Essen-Zandvliet EE, Neijens HJ. Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma. J Allergy Clin Immunol. 1987;79:653–9.CrossRefPubMed
5.
go back to reference Szefler SJ, Martin RJ, King TS, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002;109:410–8.CrossRefPubMed Szefler SJ, Martin RJ, King TS, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002;109:410–8.CrossRefPubMed
6.
go back to reference Martin RJ, Szefler SJ, King TS, et al. The predicting response to inhaled corticosteroid efficacy (PRICE) trial. J Allergy Clin Immunol. 2007;119:73–80.CrossRefPubMed Martin RJ, Szefler SJ, King TS, et al. The predicting response to inhaled corticosteroid efficacy (PRICE) trial. J Allergy Clin Immunol. 2007;119:73–80.CrossRefPubMed
7.
go back to reference Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med. 2005;172:453–9.CrossRefPubMed Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med. 2005;172:453–9.CrossRefPubMed
8.
go back to reference Boulet LP, Becker A, Be’rube’ D, et al. Canadian asthma consensus report. Can Med Assoc J. 1999;161(Suppl11):S1–62. Boulet LP, Becker A, Be’rube’ D, et al. Canadian asthma consensus report. Can Med Assoc J. 1999;161(Suppl11):S1–62.
9.
go back to reference Ungar WJ, Champman KR, Santos MT. Assessment of a medication-based asthma index for population research. Am J Respir Crit Care Med. 2002;165:190–4.PubMed Ungar WJ, Champman KR, Santos MT. Assessment of a medication-based asthma index for population research. Am J Respir Crit Care Med. 2002;165:190–4.PubMed
10.
go back to reference Vermeer H, Hendriks-Stegeman BI, Verrijn Stuart AA, et al. A comparison of in vitro bioassays to determine cellular glucocorticoid sensitivity. Eur J Endocrinol. 2004;150:41–7.CrossRefPubMed Vermeer H, Hendriks-Stegeman BI, Verrijn Stuart AA, et al. A comparison of in vitro bioassays to determine cellular glucocorticoid sensitivity. Eur J Endocrinol. 2004;150:41–7.CrossRefPubMed
11.
go back to reference Vermeer H, Hendriks-Stegeman BI, van der Burg B, et al. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab. 2003;88:277–84.CrossRefPubMed Vermeer H, Hendriks-Stegeman BI, van der Burg B, et al. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab. 2003;88:277–84.CrossRefPubMed
12.
go back to reference Vermeer H, Hendriks-Stegeman BI, van Suylekom D, et al. An in vitro bioassay to determine individual sensitivity to glucocorticoids: induction of FKBP51 mRNA in peripheral blood mononuclear cells. Mol Cell Endocrinol. 2004;218:49–55.CrossRefPubMed Vermeer H, Hendriks-Stegeman BI, van Suylekom D, et al. An in vitro bioassay to determine individual sensitivity to glucocorticoids: induction of FKBP51 mRNA in peripheral blood mononuclear cells. Mol Cell Endocrinol. 2004;218:49–55.CrossRefPubMed
13.
go back to reference Davies TH, Ning YM, Sánchez ER. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem. 2002;277:4597–600.CrossRefPubMed Davies TH, Ning YM, Sánchez ER. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem. 2002;277:4597–600.CrossRefPubMed
14.
go back to reference Wochnik GM, Ruegg J, Abel GA, et al. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem. 2005;280:4609–16.CrossRefPubMed Wochnik GM, Ruegg J, Abel GA, et al. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem. 2005;280:4609–16.CrossRefPubMed
15.
go back to reference Denny WB, Valentine DL, Reynolds PD, et al. Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding. Endocrinology. 2000;141:4107–13.CrossRefPubMed Denny WB, Valentine DL, Reynolds PD, et al. Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding. Endocrinology. 2000;141:4107–13.CrossRefPubMed
16.
go back to reference Denny WB, Prapapanich V, Smith DF, et al. Structure-function analysis of squirrel monkey FK506-binding protein 51, a potent inhibitor of glucocorticoid receptor activity. Endocrinology. 2005;146:3194–01.CrossRefPubMed Denny WB, Prapapanich V, Smith DF, et al. Structure-function analysis of squirrel monkey FK506-binding protein 51, a potent inhibitor of glucocorticoid receptor activity. Endocrinology. 2005;146:3194–01.CrossRefPubMed
17.
go back to reference Woodruff PG, Boushey HA, Dolganov GM, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci USA. 2007;104:15858–63.CrossRefPubMed Woodruff PG, Boushey HA, Dolganov GM, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci USA. 2007;104:15858–63.CrossRefPubMed
18.
go back to reference Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2006;117:522–43.CrossRefPubMed Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2006;117:522–43.CrossRefPubMed
19.
go back to reference Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull. 2000;56:1054–70.CrossRefPubMed Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull. 2000;56:1054–70.CrossRefPubMed
20.
go back to reference Pavord ID, Brightling CE, Woltmann G, et al. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999;353:2213–4.CrossRefPubMed Pavord ID, Brightling CE, Woltmann G, et al. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999;353:2213–4.CrossRefPubMed
21.
go back to reference Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–84.CrossRefPubMed Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–84.CrossRefPubMed
22.
go back to reference Adcock IM, Barnes PJ. Molecular mechanisms of corticosteroid resistance. Chest. 2008;134:394–401.CrossRefPubMed Adcock IM, Barnes PJ. Molecular mechanisms of corticosteroid resistance. Chest. 2008;134:394–401.CrossRefPubMed
23.
go back to reference McKeen HD, McAlpine K, Valentine A, et al. A novel FK506-like binding protein interacts with the glucocorticoid receptor and regulates steroid receptor signaling. Endocrinology. 2008;149:5724–34.CrossRefPubMed McKeen HD, McAlpine K, Valentine A, et al. A novel FK506-like binding protein interacts with the glucocorticoid receptor and regulates steroid receptor signaling. Endocrinology. 2008;149:5724–34.CrossRefPubMed
24.
go back to reference Reynolds PD, Ruan Y, Smith DF, et al. Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51. J Clin Endocrinol Metab. 1999;84:663–9.CrossRefPubMed Reynolds PD, Ruan Y, Smith DF, et al. Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51. J Clin Endocrinol Metab. 1999;84:663–9.CrossRefPubMed
25.
go back to reference Baptist AP, Reddy RC. Inhaled corticosteroids for asthma: are they all the same? J Clin Pharm Ther. 2009;34:1–12.CrossRefPubMed Baptist AP, Reddy RC. Inhaled corticosteroids for asthma: are they all the same? J Clin Pharm Ther. 2009;34:1–12.CrossRefPubMed
26.
go back to reference Motsinger AA, Ritchie MD, Reif DM. Novel methods for detecting epistasis in pharmacogenomics studies. Pharmacogenomics. 2007;8:1229–41.CrossRefPubMed Motsinger AA, Ritchie MD, Reif DM. Novel methods for detecting epistasis in pharmacogenomics studies. Pharmacogenomics. 2007;8:1229–41.CrossRefPubMed
27.
Metadata
Title
Dexamethasone-Induced FKBP51 Expression in Peripheral Blood Mononuclear Cells Could Play a Role in Predicting the Response of Asthmatics to Treatment with Corticosteroids
Authors
Eunyoung Chun
Hyun-Seung Lee
Bo-Ram Bang
Tae-Wan Kim
So-Hee Lee
Ju-Han Kim
Sang-Heon Cho
Kyung-Up Min
You-Young Kim
Heung-Woo Park
Publication date
01-02-2011
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 1/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9463-9

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