ROLE OF PROINFLAMMATORY CYTOKINES IN CISPLATIN-INDUCED VESTIBULAR HAIR CELL DAMAGE

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-kappa B (NF-kappa B) activation in cisplatin-treated UB/UE-1 utricular epithelial cells, We also employed immunohistochemistry to detect proinflammatory cytokines and NF-kappa B 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-kappa B 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. (C)2008 Wiley Periodicals, Inc. Head Neck 30: 1445-1456, 2008