Dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells could play a role in predicting the response of asthmatics to treatment with corticosteroids.

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.

• 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
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 31 Issue 1 Pg. 122-7 (Feb 2011) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 20853021 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Dexamethasone
• Tacrolimus Binding Proteins
• tacrolimus binding protein 5

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Animals
• Asthma (drug therapy, physiopathology)
• Dexamethasone (administration & dosage, pharmacology)
• Disease Models, Animal
• Female
• Humans
• Leukocytes, Mononuclear (drug effects, metabolism)
• Male
• Mice
• Middle Aged
• Oligonucleotide Array Sequence Analysis (methods)
• Predictive Value of Tests
• Tacrolimus Binding Proteins (genetics, metabolism, pharmacology)
• Time Factors
• Treatment Outcome
• Young Adult