gms | German Medical Science

Integrity of the auditory sensory epithelium is the foundation for an unimpaired sequence of the process of hearing. Among the great repertoire of our modern drugs there are some, which can severely affect the hair cells’ function, such as aminoglycoside antibiotics or platinum-based chemotherapeutics. Apart from drugs, also hypoxia and noise can severely damage the auditory epithelium. Since lack of the regenerative potential in hair cells results in deafness, our aim was to identify otoprotective signalling pathways.

Based on our previous research, which demonstrated otoprotective effect of interleukin-6 (IL-6), we wanted to examine in detail the mechanism behind otoprotection induced by IL-6 and IL-6 cytokine family members.

As a research model, we used explanted organs of Corti (OC) dissected from three to five-days-old Wistar rats. The OC explants were cultured in a presence or absence of 30 ng / ml of rat recombinant IL-6. Next, using subcellular fractionation and immunoblotting, we analysed the levels of signal transducer and activator of transcription 3 (STAT-3) in the cytoplasm and in the nuclei of explants. Moreover, we determined occurrence and the level of STAT-3 phosphorylation on different residues in the cytoplasm and nuclei of the explants. In addition, we assessed the phenotype of explants by staining them with fluorescently labelled phalloidin. For a read-out, we used epifluorescence and confocal microscopy. We found that the addition of IL-6 to explant cultures induces rapid translocation of STAT-3 from cytoplasm to the nucleus. In addition, IL-6 caused phospohorylation of STAT-3 on the serine- and tyrosine- residues. Translocation coincided in time with phosophorylation.

Based on above results we hypothesize that the phosphorylation and translocation of STAT-3 could be involved in the IL6-mediated, otoprotective effect.