title: Geranylgeranylacetone suppresses noise-induced expression of proinflammatory cytokines in the cochlea.
abstract: 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 3h. 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-1β (IL-1β) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamoto
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mikuriya
authors.forename: Kazuma
authors.initials: K
authors.lastname: Sugahara
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hirose
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimogori
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takii
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009622:Noise; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D004224:Diterpenes; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D014157:Transcription Factors; C031049:geranylgeranylacetone