Artikel
STAT3-mediated signaling protects the inner ear hair cells from cisplatin ototoxicity
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Veröffentlicht: | 30. Juli 2013 |
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Gliederung
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The acronym STAT3 stands for signal transducer and activator of transcription 3. STAT3-mediated signaling leads to proliferation, differentiation and survival of various cell types. During the last months, our group has been working on the assessment of STAT3’s protective potential against drug-induced ototoxicity.
As inductors of STAT3-signaling we used two different members of the Interleukin-6 (IL6) cytokine family, namely IL6 and Oncostatin M (OSM). At first, we found that simultaneous incubation with IL6 and cisplatin, our chosen ototoxic agent, partially protects inner hair cells of new born rats’ organs of Corti (OCs) from damage. In our earlier experiments, we have observed IL6 and OSM were able to influence STAT3’s subcellular localization and phosphorylation in the inner ear. To find out more about the observed protection, we have preincubated the explanted OCs with OSM or IL6 for 24h and then simultaneously incubated the tissues with the cytokine and cisplatin for another day. Hair cells were stained with Alexa Fluor 488-conjugated phalloidin and scored under epifluorescent microscope. The significance of obtained result was calculated using one-way ANOVA.
We found that preincubation of the OC explants with rat recombinant IL6 and OSM has significantly protected the inner and outer hair cells from cisplatin-induced damage in the apical, medial and basal part of the organ of Corti (n= 12 ears per condition).
From these results we can conclude that STAT3-mediated signaling plays an important role in the observed cytokine-mediated protection against cisplatin-induced ototoxicity. Our future aim is to determine, which cellular processes induced during preincubation of OC’s with IL6-famliy cytokines lead to STAT3-mediated otoprotection.