Radiation-induced NF-κB activation is involved in cochlear damage in mice via promotion of a local inflammatory response.

The radiation-induced inflammatory response is involved in radiation damage to the cochlea and causes sensorineural hearing loss (SNHL). NF-κB, as the master switch of the inflammatory response, regulates the expression of many inflammation-related genes and thus the inflammatory response. Therefore, in this study we used a mouse model to determine whether radiation-induced NF-κB activation is involved in damage to the cochlea and to investigate the underlying mechanism. Eventually, we found that NF-κB was activated after radiation of the cochleae and the activation reached a maximum at 2-6 h after radiation. And morphological analysis showed severe damage to the cochleae after radiation, but this damage was significantly ameliorated by JSH-23 (an inhibitor of NF-κB) pretreatment. Along with these morphological changes, the expression levels of proinflammatory molecules (including proinflammatory cytokines IL-6, TNF-α, COX-2 and inflammation-related proteins VCAM-1, MIP-1β) in the cochlear tissues were significantly increased after radiation, but were significantly decreased by JSH-23 pretreatment compared to radiation alone. Therefore, these results indicated that radiation-induced NF-κB activation was involved in damage to the cochleae and resultant SNHL via its promotion of the inflammatory response mediated by overexpression of some proinflammatory molecules in cochlear tissues, and inhibition of radiation-induced NF-κB was conducive to preventing such damage.