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

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• 作者：Xi Shi^a ; ^b ; ¹ ; Yanfen Dong^a ; ¹ ; Ya Li^a ; ZenLu Zhao^a ; Huan Li^a ; Shiwei Qiu^a ; Yaohan Li^a ; Weiwei Guo^b ; ^{gwent001@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yuehua Qiao^a ; ^{oto8558@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MCMV ; Inflammasome ; Caspase-1 ; SNHL
• 刊名：Journal of Otology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：10
• 期：4
• 页码：143-149
• 全文大小：1180 K

文摘

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-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.

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.