Rosiglitazone Improves Glucocorticoid Resistance in a Sudden Sensorineural Hearing Loss by Promoting MAP Kinase Phosphatase-1 Expression

Abstract EN

In this study, we investigated the role of MAP kinase phosphatase-1 (MKP-1) and rosiglitazone (RSG) in glucocorticoid resistance and glucocorticoid sensitivity, respectively, using a guinea pig model of lipopolysaccharide- (LPS-) induced sudden sensorineural hearing loss (SSHL).

The pigs were divided into control, LPS, LPS+dexamethasone (DEX), LPS+RSG, and LPS+DEX+RSG groups.

Their hearing was screened by auditory brainstem response measurement.

Immunofluorescence staining was used to identify the location of MKP-1 in the inner ear.

The expression levels of MKP-1 and the related proteins in the inner ear were detected using western blotting.

The morphological changes in the cochlea were observed via hematoxylin-eosin staining.

Severe hearing loss was observed in the LPS group, as opposed to the protection from hearing loss observed in the LPS+DEX+RSG group.

A positive correlation was observed between MKP-1 expression levels and protection from hearing loss.

RSG and DEX synergistically influenced inner ear inflammation.

In conclusion, resistance of LPS-induced SSHL guinea pig models to glucocorticoids may result from impaired MKP-1 function in inner ear tissues, induced by glucocorticoids, impairing the inhibition of inflammation.

Our findings present novel targets to develop potential therapeutics to treat inflammatory diseases of the inner ear.