Transforming growth factor beta expression during an inner ear immune response.
OBJECTIVE
The involvement of transforming growth factor beta (TGF-beta), a strong mediator of fibrogenesis, during cochlear immune responses was investigated.


METHODS
An inner ear adaptive immune response to antigen was created in mice that were painlessly sacrificed 3 to 48 hours and 7 days after initiation of the immune response. The cochleas were assayed by immunocytochemistry for TGF-beta and latency-associated peptide (LAP).


RESULTS
We found LAP expressed in normal cochleas and the endolymphatic sac, in the small round cells in the cochlear scalae and the mesothelial cells under the basilar membrane, and in the endolymphatic sac perisaccular area. We found TGF-beta expressed in infiltrated, inflammatory cells in the scalae and the endolymphatic sac lumen 3 hours after cochlear antigen challenge. At this time, LAP immunoreactivity was decreased. This rapid shift in immunoreactivity provides evidence for activation of TGF-beta during an immune response. This reversal of expression persisted for 48 hours, but conditions reverted to normal after 7 days. Surgical controls did not show TGF-beta expression.


CONCLUSIONS
We conclude that TGF-beta activation occurs in the early phase of a cochlear adaptive immune response and is down-regulated as the response resolves. This finding suggests that the process of cochlear fibrosis starts early and that proper treatment could prevent cochlear fibrosis.
Satoh
Hitoshi
H
Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, USA.
Billings
Peter
P
Firestein
Gary S
GS
Harris
Jeffrey P
JP
Keithley
Elizabeth M
EM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003051:Cochlea / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D007762:Labyrinthitis / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D015415:Biomarkers; D016212:Transforming Growth Factor beta