Toxicologic Pathology · 2005 · 38 citations · 30 references
Life SciencesCell BiologyPathobiologyCell JunctionsCellular PathologySignal TransductionDigestive PhysiologyGastrointestinal DiseaseGastrointestinal InflammationGastrointestinal PathologyGastrointestinal PathophysiologyMucosal InflammationGastric HistologyGastrointestinal MucosaGastrointestinal Mucosal DamageGastrointestinal UlcerationIntestinal HistologyIntestinal Mucosal InjuryIntestinal Villi MicroanatomyIsoform Differential Expression
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.
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