Shi Xi, Dong Yanfen, Li Ya, Zhao ZenLu, Li Huan, Qiu Shiwei, Li Yaohan, Guo Weiwei, Qiao Yuehua
The Institute of Audiology and Speech Science of Xuzhou Medical Collage, Xuzhou 221004, China.
Department of Otolaryngology, Head & Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing 100853, China.
J Otol. 2015 Dec;10(4):143-149. doi: 10.1016/j.joto.2015.12.001. Epub 2016 Jan 6.
To identify presence of inflammasome activated in mouse cochlea with sensorineural hearing loss (SNHL) caused by cytomegalovirus (CMV) infection.
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.
In the mouse model of CMV induced SNHL, inflammasome related kinase Caspase-1 and downstream inflammatory factor IL-1β 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 TNF-α. 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.
We have shown that inflammasome as a novel inherent immunity mechanism may contribute to hearing impairment.
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.
确定在巨细胞病毒（CMV）感染所致感音神经性听力损失（SNHL）的小鼠耳蜗中是否存在激活的炎性小体。
以2000 pfu病毒滴度将巨细胞病毒（MCMV）注射到新生BALB/c小鼠的右侧大脑半球。在21天时测试听觉脑干反应（ABR）以评估听力。进行组织病理学研究以确认内耳中MCMV感染细胞的定位。通过免疫荧光、定量实时PCR和蛋白质印迹法评估炎性小体相关因子的表达。
在CMV诱导的SNHL小鼠模型中，发现炎性小体相关激酶半胱天冬酶-1以及下游炎性因子白细胞介素-1β和白细胞介素-18在CMV感染后在耳蜗中增加并被激活。这些因子可进一步上调白细胞介素-6和肿瘤坏死因子-α的表达。这些炎性因子具有神经毒性，可能导致听力损害。此外，我们还检测到在CMV感染的耳蜗螺旋神经节中聚集的AIM2蛋白显著增加。
我们已经表明炎性小体作为一种新的固有免疫机制可能导致听力损害。
我们的数据表明炎性小体在小鼠内耳中因CMV感染而组装。我们揭示了CMV诱导的SNHL中一个新的病理事件，涉及小鼠耳蜗中炎性小体的激活。此外，我们已经表明炎性小体可能是预防和治疗CMV相关SNHL的新靶点。
