Intratympanic dexamethasone up-regulates Fkbp5 in the cochleae of mice in vivo.
CONCLUSIONS
Quantitative, real-time RT-PCR demonstrated that intratympanic dexamethasone significantly up-regulates the expression of Fkbp5 in cochleae of mice in vivo. The immunohistochemistry results showed fundamentally ubiquitous expression of Fkbp5 in cochlear structures, with relatively strong expression in type 4 fibrocytes and weak signal in the inner hair cells. These data indicate that dexamethasone regulates gene expression at the level of transcription in vivo and that this process is basically ubiquitous in the cochlea.


OBJECTIVE
To demonstrate that intratympanically applied dexamethasone up-regulates Fkbp5 in the cochlea in vivo.


METHODS
Dexamethasone or control saline were intratympanically applied to adult C57/BL6 mice and dexamethasone-dependent changes in the levels of Fkbp5 expression in the cochlea were analyzed using quantitative real-time RT-PCR. The expression pattern of Fkbp5 in cochlea was investigated by immunohistochemistry in mice that were administered dexamethasone and in controls.


RESULTS
Quantitative real-time RT-PCR demonstrated significant increases of Fkbp5 expression levels in cochleae of dexamethasone-treated mice as compared with controls at 12 h after application (244.8 ± 155.5, n = 5 vs 100.0 ± 3.0, n = 6, p < 0.01). Immunohistochemistry showed fundamentally ubiquitous expression of Fkbp5 in cochlear structures, with some strongly positive fibrocytes in the spiral ligaments and weak immunoreactivity in the inner hair cells. Distribution of Fkbp5 signaling was not different between the dexamethasone-treated group and controls.
Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacy, Japan. maedayj@yahoo.co.jp
Yukihide
Y
Maeda
Kunihiro
K
Fukushima
Shin
S
Kariya
Yorihisa
Y
Orita
Kazunori
K
Nishizaki
D000287:Administration, Topical; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D018841:HSP90 Heat-Shock Proteins; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D014432:Tympanic Membrane; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
D003907:Dexamethasone; D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5