Relationship of Glucocorticoid Receptor Expression in Peripheral Blood Mononuclear Cells and the Cochlea of Guinea Pigs and Effects of Dexamethasone Administration

Ling Lu,Yanhong Dai,Qin Wu,Wandong She,Feng Chen,Wenjie Yuan,Xiaoping Du,Xiuling Zhang

doi:10.1371/journal.pone.0056323

Ling Lu, Yanhong Dai + Show 6 more

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https://doi.org/10.1371/journal.pone.0056323

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Abstract

BackgroundGlucocorticoids (GCs) are widely used to treat sudden sensorineural hearing loss (SSNHL) and significantly improve hearing. However, GC insensitivity has been observed in some patients of SSNHL.ObjectiveTo study the correlation between GR expression in peripheral blood mononuclear cells (PBMCs) and in the cochlea of guinea pigs at mRNA and protein levels.MethodsOne group of guinea pigs received dexamethasone (10 mg/kg/day) intraperitoneally for 7 consecutive days (dexamethasone group), and another group of guinea pigs received normal saline (control group). Real time PCR and Western blotting were used to detect the expression of GR mRNA and GR protein in PBMCs and the cochleae.ResultsThe GR mRNA and GR protein were detected in both PBMCs and the cochlear tissue of guinea pigs. GR mRNA and GR protein levels in PBMCs were positively correlated with those in the cochlea. The expression of GR mRNA and GR protein was significantly increased in the dexamethasone group compared to the control group.ConclusionsLevels of GR mRNA and GR protein in the PBMCs were positively correlated with those in the cochlea of guinea pigs. Systemic dexamethasone treatment can significantly up-regulate GR expression in PBMCs and in the cochlea. Measurement of the GR level in PBMCs could be used as an indicator of GR level in the cochlea.

Highlights

The cause of sudden sensorineural hearing loss (SSNHL) is still unclear, various infective, vascular, and immune causes have been proposed [1]
To test the hypothesis that glucocorticoid receptor (GR) levels in the cochlea may be related to that in peripheral blood mononuclear cells (PBMCs), quantitative real-time PCR and western blots were used as complementary approaches to detect the expression levels of GR mRNA and GR protein in both PBMCs and cochleae from 32 cases of healthy guinea pigs
Comparative analyses of GR expression levels in dexamethasone group (DG) and control group (CG) were conducted in order to investigate how the systemic administration of the glucocorticoid, dexamethasone, impacted GR expression in PBMCs and cochleae of guinea pigs

Summary

Introduction

The cause of sudden sensorineural hearing loss (SSNHL) is still unclear, various infective, vascular, and immune causes have been proposed [1]. Glucocorticoids (GCs) are widely used to treat SSNHL and significantly improve hearing [1,2]. GCs could inhibit several inflammatory mediators and increase cochlear blood flow to prevent hair cell damage caused by inflammation and ischemia in the inner ear [3,4,5]. Ligand-bound GR interacts with regulatory elements in the genome to induce or repress transcription of hundreds of target genes to control regulatory networks in fetal development, metabolism, cognition and inflammation [13,14,15]. Glucocorticoids (GCs) are widely used to treat sudden sensorineural hearing loss (SSNHL) and significantly improve hearing. GC insensitivity has been observed in some patients of SSNHL

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