Upregulation of the Major Histocompatibility Complex (MHC-I) in Auditory Hair Cells Exposed To Interferon Alpha

Previous studies have reported hearing loss in patients undergoing interferon-alpha (IFN-α) therapy. The mechanisms by which IFN-α causes hearing loss remain poorly understood. This study was designed to investigate if the immune reaction is one of these mechanisms. Real time-PCR was used to determine the expression of the major histocompatibility class-I (MHC-I) in HEI-OC1 auditory hair cell line. This gene is a marker for an immune response and it is known as H2K1 gene. The cochlear cells were treated by IFN-α (0, 200 & 2000U/ml) for 6, 12, 24 & 48 Hrs. Differential gene expression patterns encoding IFN-α-1, IFN-γ and H2K1 (MHC-I) were assessed by real-time PCR. The results revealed significant expression of the MHC-I gene in a dose- and time-dependent manner. This outcome indicates that IFN-α led to initiation of an immune reaction in the cochlear cell line. Therefore, the current in-vitro study indicates that the immune reaction might be the underlying mechanism of the hearing impairment observed in patients undergoing IFN-α therapy. These results imply that pre-treatment hearing evaluation and close monitoring of hearing function in patients undergoing long-term high-dose of IFN-α therapy are necessary to avoid or to minimize its adverse effect on hearing. Abbreviations: IFNs: interferons; IFN-α: interferon-alpha; IFN-β: interferon-beta; IFN- γ: interferon-gama; rt-PCR:real time polymerase chain reaction;HEI-OC: House Ear Institute- organ of Corti; STATs: signal transducers and activators of transcription; JAK: Janus Kinases; R1: receptor1;R2: receptor2; ISGF-3: interferon-stimulated gene factor-3; ISRE: interferon stimulated response element; GAS: gamma activating sequence; NK: natural killer cells; DCs: dendritic cells; CD:clusters of differerntiation; KLH: keyhole limpet hemocyanin; ES:endolymphatic sac; FACS: fluoresce-activated cell sorter; SNHL: sensorineural hearing loss; FBS: fetal bovine serum.