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


CONCLUSIONS
Dexamethasone-induced FKBP51 expression in PBMCs may be a reliable and practical biomarker in predicting the response to CSs in asthmatics.
Chun
Eunyoung
E
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongondong, Chongno-gu, Seoul 110-744, Republic of Korea.
Lee
Hyun-Seung
HS
Bang
Bo-Ram
BR
Kim
Tae-Wan
TW
Lee
So-Hee
SH
Kim
Ju-Han
JH
Cho
Sang-Heon
SH
Min
Kyung-Up
KU
Kim
You-Young
YY
Park
Heung-Woo
HW
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011237:Predictive Value of Tests; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
D000305:Adrenal Cortex Hormones; D003907:Dexamethasone; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5