Expressions of cyclooxygenase 1 and 2 in endotoxin-induced otitis media with effusion in the rat.
OBJECTIVE
Recently, a selective COX-2 inhibitor was developed and used for reducing the levels of inflammation-inducing prostaglandin (PG) whilst not inhibiting the release of protective PG by COX-1. COX-1 may be the critical isoform required for the production of PG with a homeostatic function, whereas COX-2 may be the main contributor to PG production in inflammation. The purpose of this study was to investigate COX-1 and 2 expressions in experimental endotoxin-induced OME in rats and to quantify their temporal expressions.


METHODS
In a rat model, lipopolysaccharides (LPS) were inoculated into the middle ear cavity. Middle ear mucosa and temporal bone were samples at 0, 1, 3, 6, and 12h, and on days 1, 3 and 7 after instilling either LPS or sterile PBS. RT-PCR, Western blotting and immunohistochemical staining were performed to determine the expressions of COX-1 and COX-2.


RESULTS
COX-1 mRNA and protein were detected in normal middle ear mucosa but their levels did not change after endotoxin instillation. However, COX-2 was not identified in normal middle ear mucosa, but COX-2 mRNA was maximally increased at 6h after endotoxin instillation and COX-2 protein was maximally increased at 12h. COX-2 expression, by immunohistochemical staining, was identified only at 12h after endotoxin injection.


CONCLUSIONS
In this study, the basal expressions of COX-1 and COX-2 mRNA and protein in middle ear mucosa, as well as their regulations by endotoxin were investigated. COX-1 was not induced in middle ear mucosa by endotoxin whereas COX-2 was induced within 12h of stimulation. Our findings indicate that COX-2 inhibitor administration for the relief of inflammation should be considered within 12h of the initiation of an inflammatory process. These findings may provide an understanding of the mechanisms regulating PG formation in infection of the middle ear cavity.
Cho
Jae-Gu
JG
Department of Otorhinolaryngology-Head and Neck Surgery, Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
Lee
Eun Soo
ES
Woo
Jeong-Soo
JS
Lee
Heung-Man
HM
Jung
Hak Hyun
HH
Hwang
Soon Jae
SJ
Chae
Sung Won
SW
D000818:Animals; D015153:Blotting, Western; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004432:Ear, Middle / Q000201:enzymology*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D009092:Mucous Membrane / Q000201:enzymology; D010034:Otitis Media with Effusion / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001613:beta 2-Microglobulin / Q000378:metabolism
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2