Age-dependent changes in the regulation of cyclooxygenases in the gastrointestinal tract after gram-negative endotoxemia.

Background: Cyclooxygenases (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. Methods:Stomach, 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. Results: Stomach, 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). Conclusions: In 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.