Role of proinflammatory cytokines in cisplatin-induced vestibular hair cell damage

✍ Scribed by Hyung-Jin Kim; Hong-Seob So; Jeong-Han Lee; Channy Park; Jin-Bin Lee; Myung-Ja Youn; Se-Jin Kim; Sei-Hoon Yang; Kang-Min Lee; Kang-Beom Kwon; Byung-Hyun Park; Raekil Park

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 443 KB
• Volume: 30
• Category: Article
• ISSN: 1043-3074
• DOI: 10.1002/hed.20892

✦ Synopsis

Abstract

Background.

Cisplatin causes the impairment of inner ear functions, including hearing and balance, through the involvement of a number of mechanisms. However, no laboratory studies have been performed on involvement of inflammation‐related events in cisplatin‐mediated vestibular dysfunction.

Methods.

We evaluated the secretion of proinflammatory cytokines and nuclear factor‐κB (NF‐κB) activation in cisplatin‐treated UB/UE‐1 utricular epithelial cells. We also employed immunohistochemistry to detect proinflammatory cytokines and NF‐κB expression in cisplatin‐injected mice.

Results.

Productions of proinflammatory cytokines significantly caused the death of UB/UE1 cells by cisplatin. Pharmacologic inhibition of mitogen‐activated protein (MAP) kinase/ERK kinase‐1 (MEK1) or extracellular signal‐regulated kinase (ERK) significantly attenuated the death of UB/UE1 cells caused by cisplatin and proinflammatory cytokines. Immunohistochemical studies revealed an increase in the expression of proinflammatory cytokines and NF‐κB in both the cristae ampullae and utricle of cisplatin‐injected mice.

Conclusions.

These results suggest that proinflammatory cytokines may play an important role in the pathogenesis of cisplatin‐mediated vestibulotoxicity. © 2008 Wiley Periodicals, Inc. Head Neck, 2008