Geranylgeranylacetone suppresses noise-induced expression of proinflammatory cytokines in the cochlea

Objective: Heat shock transcription factor 1 (HSF1) is a master regulator of heat shock response, and also inhibits expression of inflammatory cytokines directly or indirectly. Here, we examined effects of HSF1 activation on the expression of proinflammatory cytokines in mouse cochlea after exposure to noise. Methods: Male CBA/N mice with normal Preyer's reflex were exposed to intense noise for 3 h. Three hours after noise exposure, bilateral cochleae were removed and expression of major inflammatory cytokines was examined. Results: We found that interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) expression increased significantly after noise exposure, and the expression was suppressed significantly in mice administered with geranylgeranylacetone (GGA), which activates HSF1. Seven days after noise exposure, thresholds for auditory brainstem response were elevated, and GGA administration significantly suppressed this elevation. Conclusion: These results suggest that HSF1-mediated suppression of proinflammatory cytokines in the cochlea by GGA administration could be an important means of inner ear protection. (C) 2011 Elsevier Ireland Ltd. All rights reserved.