Cisplatin ototoxicity involves cytokines and STAT6 signaling network  

作　　者：Hyung-Jin Kim Gi-Su Oh Jeong-Han Lee Ah-Ra Lyu Hye-Min Ji Sang-Heon Lee Jeho Song Sung-Joo Park Yong-Ouk You Jeong-Dug Sul Channy Park Sang-Young Chung Sung-Kyun Moon David J Lim Hong-Seob So Raekil Park 

机构地区：[1]Vestibulocochlear Research Center & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749, Korea [2]Department of Otolaryngology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea [3]Department of Beauty Design, Wonkwang University, Iksan, Jeonbuk 570-749, Korea [4]Department of Herbology, School of Oriental Medicine, Wonk- wang University, Iksan, Jeonbuk 570-749, Korea [5]Department of Oral Biochemistry, School of Dentistry, Wonkwang University, Iksan, Jeonbuk 570-749, Korea [6]College of Sport Science, Chung-Ang University, Seoul, Korea [7]Department of Audiology, Nam- bu University, Gwangju 506-824, Korea [8]Department of Surgery, Chonnam National University Medical School, Gwang/u 560- 182, Korea [9]Gonda Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, CA 90057, USA

出　　处：《Cell Research》2011年第6期944-956,共13页细胞研究（英文版）

摘　　要：We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c （wild type, WT） and STAT4-/-, but not in STAT6-/- mice. Moreover, the expression levels of the protein and mRNA of pro- inflammatory cytokines, including TNF-u, IL-Ⅱ, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4-/-, but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-j- mice were intact after treatment with cisplatin, where- as those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory ceils, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphoryla- tion of STAT6 by binding with IL-4 receptor alpha and IL-13Rul. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.

关 键 词：CISPLATIN OTOTOXICITY STAT INFLAMMATION apoptosis 

分 类 号：Q522[生物学—生物化学] S856.9[农业科学—临床兽医学]