Age‐Dependent Changes in the Regulation of Cyclooxygenases in the Gastrointestinal Tract After Gram‐Negative Endotoxemia

Abstract

ABSTRACTBackgroundCyclooxygenases (COXs) modulate prostaglandin synthesis in the gastrointestinal tract. Prostaglandins have been shown to have a cytoprotective effect on bowel mucosa in adults, but no similar data are available in neonates. Thus, the purpose of the current study was to evaluate age‐dependent changes in gastrointestinal tract COX regulation after Escherichia coli lipopolysaccharide exposure in rats.MethodsStomach, small bowel, and large bowel COX‐1 and COX‐2 mRNA levels (reverse transcription polymerase chain reaction technique) and protein content (Western blot) were obtained from neonates (younger than 3 days old) and adult rats 18 hours after exposure to E. coli O111:B4 lipopolysaccharide toxin. Untreated animals served as controls.ResultsStomach, small bowel, and large bowel tissue COX‐1 mRNA levels in the newborn were significantly lower (P < 0.01) than in the adult. No age‐dependent differences were found for COX‐2 mRNA levels. After lipopolysaccharide exposure, no significant changes in COX‐1 levels were seen at either age, whereas COX‐2 mRNA levels were increased only in the stomach for both ages. Western blot analysis of small bowel tissue for COX‐1 and COX‐2 showed no lipopolysaccharide‐induced changes in protein content, but the COX‐1 content was significantly lower in the newborn (P < 0.01).ConclusionsIn the rat, COX expression in the gastrointestinal tract is regulated in an age‐dependent fashion. Lower COX‐1 expression and a lack of observable increase in COX‐2 mRNA levels in the newborn small bowel after endotoxemia may render the bowel more susceptible to bowel injury early in life.