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Inflammasome activation in mouse inner ear in response to MCMV induced hearing loss

查看全文 作  者:Xi [1,2]Shi;Yanfen [1]Dong;Ya [1]Li;ZenLu [1]Zhao;Huan [1]Li;Shiwei [1]Qiu;Yaohan [1]Li;Weiwei [2]Guo;Yuehua [1]Qiao 高影响力作者 机构地区:[1]The Institute of Audiology and Speech Science of Xuzhou Medical Collage;[2]Department of Otolaryngology, Head&Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital高影响力机构 出  处:《Journal of Otology》索引2015年第10卷第4期,共7页高影响力期刊 基  金:supported by the National Natural Science Foundation of China [grant numbers 31300624];Postdoctoral Science Foundation of China [grant numbers 2015M571818];Six Major Categories Talent [grant numbers 2014-WSN-043];Innovation and Entrepreneurship Training Program for College Student in Jiangsu Province [grant numbers 201510313003Z] 摘  要:Objective: To identify presence of inflammasome activated in mouse cochlea with sensorineural hearing loss(SNHL) caused by cytomegalovirus(CMV) infection.Method: MCMV was injected into the right cerebral hemisphere in neonatal BALB/c mice at 2000 pfu virus titers. Auditory brainstem responses(ABRs) were tested to evaluate hearing at 21 days. Histopathological studies were conducted to confirm localizations of MCMV infected cells in the inner ear. Expression of inflammasome related factors was assessed by immunofluorescence, Quantitative real-time PCR and Western blotting.Results: In the mouse model of CMV induced SNHL, inflammasome related kinase Caspase-1 and downstream inflammatory factor IL-1b and IL-18 were found increased and activated after CMV infection in the cochlea. These factors could further up-regulate expression of IL-6 and TNFa. These inflammatory factors are neurotoxicity and may contribute to hearing impairment. Furthermore, we also detected significantly increased AIM2 protein that accumulated in the SGN of cochleae with CMV infection.Significance: We have shown that inflammasome as a novel inherent immunity mechanism may contribute to hearing impairment.Conclusion: Our data indicate that imflammasome assemble in mouse inner ear in response to CMV infection. We have revealed a novel pathology event in CMV induced SNHL involving activation of inflammasome in mouse cochlea. Additionally, we have shown that inflammasome may be a novel target for prevention and treatment of CMV related SNHL. 关 键 词:MCMV INFLAMMASOME CASPASE-1 SNHL
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