Artikel
Influence of interleukin-6 on cisplatin-induced auditory hair cell loss
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Veröffentlicht: | 6. Juli 2010 |
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Gliederung
Text
Damaged auditory epithelium and consequent hearing loss is a side effect of cancer chemotherapy with cisplatin. Recent reports implicated a significant role of pro-inflammatory cytokines (IL1β, IL6 and TNFα) in the cisplatin-induced ototoxicity. The effect of two pro-inflammatory cytokines on the auditory epithelium, namely IL1β and TNFα was previously studied. Here, we explored the effect of IL6 on the cochlear membranous tissues. As an experimental model, we used the explanted organs of Corti (OCs) dissected from Wistar rats (p3–p5). First, we positively confirmed the expression of IL6 receptor in the OC, by means of RT-PCR and immunofluorescence. Second, using immunoblotting and confocal microscopy we demonstrated that STAT3 (essential component of IL6 signaling pathway) is well expressed by the auditory hair cells, supporting cells and neurons. We also found that the addition of recombinant IL6 (rIL6) to the OC explant cultures induces transient phosporylation of STAT3 on tyrosine residue. Next, to determine the effect of IL6 on the viability of auditory epithelium, we cultured the OC explants with the rIL6 (0.3, 3, 30 and 90 ng/ml). We found no changes in number or morphology of the auditory hair cells. Subsequent experiments revealed that the addition of rIL6 (30 ng/ml) to OC explants cultured with cisplatin (15 µM) has not exacerbated the loss of hair cells, as compared to cisplatin-treated controls. In contrast, more auditory hair cells have survived in the presence of IL6. The IL6-induced cytoprotection was observed only in the apical part of the OC and only in the inner hair cells. Taken together, our results suggest that IL6 can signal in the rat OC. Further, IL6-induced signaling pathway may have otoprotective qualities when used together with cisplatin in vitro.
References
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