Burn injury with infection alters prostaglandin E-2 synthesis and metabolism

Objective: The aim of this study was to examine the relationship between pr ostaglandin synthesis and prostaglandin degradation in a model of burn inju ry with infection, Methods: Male B2D6F1 mice were assigned to control, burn (16% dorsal scald burn), or burn with infection (burn with topical application of 1,000 colon y forming units of Pseudomonas aeruginosa) groups. Lung tissue was harveste d at 1, 2, and 3 days after burn injury and subsequently processed for tota l RNA and protein. Northern and Western blot analyses were used to examine differences in cycooxygenase 2 (COX-2) and prostaglandin 15-OH dehydrogenas e (PGDH) protein and mRNA expression. Total RNA was probed with the ribopro be for murine PGDH and COX-2 and the 100,000 g protein fraction was inmunob lotted by using an rabbit anti-murine PGDH and anti-murine COX-2 antibody, Results: COX-2 expression was elevated in the burn with infection animals o n day 1 and day 2 after burn injury. At these time points in the burn + inf ection group, PGDH was significantly depressed. Burn injury increased COX-2 expression on day 1, but by day 2, COX-2 expression had decreased to contr ol values. A corresponding increase in PGDH expression was observed on day 2 in the burned mice. The mRNA expression of COX-2 was followed by a simila r increase in COX-2 protein expression at all time points in the injured an imals, This was not the case with PGDH expression. On day 1, PGDH mRNA expr ession was depressed in the burn with infection mice with no change in PGDH protein expression. This finding indicates that PGDH is subject to regulat ion at both the transcriptional and posttranscriptional levels. Conclusion: Burn wound infection depressed both PGDH mRNA and protein expre ssion and increased COX-2 mRNA and protein expression, Therefore, increases in circulating prostaglandin E-2 levels during septic injury are derived f rom alterations in synthesis and degradation of prostaglandin E-2.