Differential expression of COX-1 and COX-2 in the gastrointestinal tract of the rat.
The aim of this study was to use immunohistochemistry with morphometry to investigate COX-1 and COX-2 expression in the normal rat gastrointestinal (GI) tract and examine if sites of ulceration previously observed with long-term COX-2 inhibitor administration in mice correlate with differential COX-1/COX-2 expression. COX-2 positive cells were observed predominantly in the apical lamina propria of intestinal villi with fewer cells in the mucosal epithelium. The highest level of COX-2 expression was observed at the ileocaecal junction (ICJ). COX-2 expression was also present in parasympathetic ganglia of the submucosa and muscularis. In the stomach, the highest grade of COX-2 expression was observed in the apical lamina propria of the fundus adjacent to the junctional ridge. In contrast, COX-1 positive cells within the lamina propria were evenly distributed along the GI tract but were present in higher numbers than COX-2 positive cells. The mean level of COX-1 expression at the ICJ was not significantly different from the ileum and caecum. Evidence that the highest level of COX-2 expression in normal rats is located on the ileal side of the ICJ provides the first mechanism to explain spontaneous ulceration and perforation of the distal ileum in COX-2 -/- animals.
Haworth
Richard
R
Department of Pathology, Safety Assessment, GlaxoSmithKline Research and Development Ltd., Ware, Herts SG12 0DP, United Kingdom. richard.i.haworth@gsk.com
Oakley
Keli
K
McCormack
Nicola
N
Pilling
Andrew
A
D000818:Animals; D002432:Cecum / Q000166:cytology / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D053331:Ectodysplasins; D005260:Female; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism*; D007082:Ileum / Q000166:cytology / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016610:Tissue Embedding / Q000379:methods
D053331:Ectodysplasins; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat