Burn injury with infection alters prostaglandin E2 synthesis and metabolism.
OBJECTIVE
The aim of this study was to examine the relationship between prostaglandin synthesis and prostaglandin degradation in a model of burn injury 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 colony forming units of Pseudomonas aeruginosa) groups. Lung tissue was harvested at 1, 2, and 3 days after burn injury and subsequently processed for total RNA and protein. Northern and Western blot analyses were used to examine differences in cyclooxygenase 2 (COX-2) and prostaglandin 15-OH dehydrogenase (PGDH) protein and mRNA expression. Total RNA was probed with the riboprobe for murine PGDH and COX-2 and the 100,000g protein fraction was immunoblotted 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 on day 1 and day 2 after burn injury. At these time points in the burn + infection group, PGDH was significantly depressed. Burn injury increased COX-2 expression on day 1, but by day 2, COX-2 expression had decreased to control 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 similar increase in COX-2 protein expression at all time points in the injured animals. This was not the case with PGDH expression. On day 1, PGDH mRNA expression was depressed in the burn with infection mice with no change in PGDH protein expression. This finding indicates that PGDH is subject to regulation at both the transcriptional and posttranscriptional levels.


CONCLUSIONS
Burn wound infection depressed both PGDH mRNA and protein expression and increased COX-2 mRNA and protein expression. Therefore, increases in circulating prostaglandin E2 levels during septic injury are derived from alterations in synthesis and degradation of prostaglandin E2.
Hahn
E L
EL
The Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Tai
H H
HH
He
L K
LK
Gamelli
R L
RL
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002056:Burns / Q000150:complications*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis* / Q000235:genetics*; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics*; D008168:Lung / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics*; D011552:Pseudomonas Infections / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D014158:Transcription, Genetic / Q000235:genetics; D014946:Wound Infection / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
D007527:Isoenzymes; D012333:RNA, Messenger; D006911:Hydroxyprostaglandin Dehydrogenases; C038661:15-hydroxyprostaglandin-D dehydrogenase (NADP+); D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone