시스플라틴에 의한 염증성 사이토카인의 청각유모세포 사멸 효과 (The Effects of Pro-inflammatory Cytokines by Cisplatin on the Death of Sensory Hair Cells)

서지정보

· 발행기관 : 한국생명과학회
· 수록지 정보 : 생명과학회지 / 18권 / 4호 / 542 ~ 549페이지
· 저자명 : 이정한, 박래길, 박찬희

초록

Cisplatin (cis-diamminedichloroplatinum Ⅱ: CDDP) is the most widely used anticancer drug against a variety of human neoplasms. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. Even though a number of evidences in cytotoxic mechanism of cisplatin have been suggested, the role of pro-inflammatory cytokines in cisplatin cytotoxicity of auditory cells has not yet been demonstrated. Herein our data clearly demonstrated that cisplatin decreased the viability of HEI-OC1 auditory cells, which was inhibited by the addition of neutralizing anti-TNF-α, anti-IL-1β and anti-IL-6 antibodies. Consistently, Neutralization with antibodies against pro-inflammatory cytokines ameliorated the cell death and disarrangement of cochlea hair cell layers in the rat primary cochlear explants which were treated with cisplatin. Furthermore, exogeneous supplementation with free radical scavengers, including GSH and NAC, significantly prevented the cytotoxicity of cisplatin in the rat primary cochlea explants. We also observed that TNF-α was predominantly expressed in Deiters and Hensen's cells located in hair cell zone of cisplatin-treated cochlear explants. These findings suggest that pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, may play a pivotal role in the pathophysiology of hair cell damages caused by ototoxic drug cisplatin.

영어초록

Cisplatin (cis-diamminedichloroplatinum Ⅱ: CDDP) is the most widely used anticancer drug against a variety of human neoplasms. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. Even though a number of evidences in cytotoxic mechanism of cisplatin have been suggested, the role of pro-inflammatory cytokines in cisplatin cytotoxicity of auditory cells has not yet been demonstrated. Herein our data clearly demonstrated that cisplatin decreased the viability of HEI-OC1 auditory cells, which was inhibited by the addition of neutralizing anti-TNF-α, anti-IL-1β and anti-IL-6 antibodies. Consistently, Neutralization with antibodies against pro-inflammatory cytokines ameliorated the cell death and disarrangement of cochlea hair cell layers in the rat primary cochlear explants which were treated with cisplatin. Furthermore, exogeneous supplementation with free radical scavengers, including GSH and NAC, significantly prevented the cytotoxicity of cisplatin in the rat primary cochlea explants. We also observed that TNF-α was predominantly expressed in Deiters and Hensen's cells located in hair cell zone of cisplatin-treated cochlear explants. These findings suggest that pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, may play a pivotal role in the pathophysiology of hair cell damages caused by ototoxic drug cisplatin.

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