The relationship between mucosal cyclooxygenase-2 (COX-2) expression and experimental radiation-induced mucositis.
Although cycloooxygenase-2 (COX-2) is upregulated by factors associated with oral mucositis, its role in the pathogenesis of mucositis has not been studied. We investigated the kinetics of mucosal COX-2 expression following radiation exposure, and assessed its relationship to the development of oral mucositis in an established animal model using immunohistochemical endpoints. While little or no COX-2 expression was observed in unirradiated mucosa or in tissue taken 2 days after radiation, COX-2 expression was dramatic on days 10 and 16, especially in submucosal fibroblasts and endothelium. The kinetics of COX-2 expression paralleled mucositis severity. A burst of angiogenic activity was seen on day 21 following peak COX-2 expression. The kinetics of COX-2 expression relative to mucositis progression suggests that COX-2 is not a primary driver of radiation injury, but instead plays an amplifying role.
Sonis
S T
ST
Division of Oral Medicine, Oral and Maxillofacial Surgery and Dentistry, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, USA. ssonis@partners.org
O'Donnell
K E
KE
Popat
R
R
Bragdon
C
C
Phelan
S
S
Cocks
D
D
Epstein
J B
JB
D000818:Animals; D006224:Cricetinae; D051546:Cyclooxygenase 2; D005347:Fibroblasts / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000098:blood supply / Q000201:enzymology / Q000528:radiation effects; D009389:Neovascularization, Pathologic / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000201:enzymology*; D013280:Stomatitis / Q000201:enzymology* / Q000209:etiology; D015854:Up-Regulation
D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases