Role of proinflammatory cytokines in cisplatin-induced vestibular hair cell damage.
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-kappaB (NF-kappaB) activation in cisplatin-treated UB/UE-1 utricular epithelial cells. We also employed immunohistochemistry to detect proinflammatory cytokines and NF-kappaB 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-kappaB 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 vestibulo-toxicity.
Kim
Hyung-Jin
HJ
Vestibulocochlear Research Center and Department of Microbiology, School of Medicine, Wonkwang University, Jeonbuk, Korea.
So
Hong-Seob
HS
Lee
Jeong-Han
JH
Park
Channy
C
Lee
Jin-Bin
JB
Youn
Myung-Ja
MJ
Kim
Se-Jin
SJ
Yang
Sei-Hoon
SH
Lee
Kang-Min
KM
Kwon
Kang-Beom
KB
Park
Byung-Hyun
BH
Park
Raekil
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D018069:Hair Cells, Vestibular / Q000187:drug effects* / Q000276:immunology*; D034381:Hearing Loss / Q000139:chemically induced / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology
D000970:Antineoplastic Agents; D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; D002945:Cisplatin