Molecular mechanisms contributing to necrotizing enterocolitis.
OBJECTIVE
To examine the cellular mechanisms involved in the pathogenesis of necrotizing enterocolitis (NEC).


BACKGROUND
Necrotizing enterocolitis is a major cause of death and complications in neonates; the cellular mechanisms responsible for NEC are unknown. The inducible form of cyclooxygenase (i.e., COX-2) is activated by the transcription factor nuclear factor (NF)-kappaB and is thought to play a role in inflammation.


METHODS
Segments of perforated and adjacent uninvolved small intestine from neonates with NEC were analyzed for COX-2 expression by immunohistochemistry. NEC was induced in weanling (18 days old) rats by occlusion of superior mesenteric vessels for 1 hour and intraluminal injection of platelet activating factor (50 micro/kg). Small intestine was harvested for protein extraction. Western immunoblot was performed to determine expression of COX-2. Gel shift assays were performed to assess NF-kappaB binding activity.


RESULTS
Immunohistochemical analysis showed increased COX-2 protein expression in the perforated intestinal sections of all 36 neonates but not in adjacent normal intestine. Increased expression of COX-2 protein and NF-kappaB binding activity was noted in the small intestine of weanling rats at 0 and 3 hours after induction of NEC.


CONCLUSIONS
Increased COX-2 expression was identified in all neonatal intestinal segments resected for perforated NEC. In addition, a coordinate induction of COX-2 expression and NF-kappaB binding was noted in a rodent model of NEC. These findings suggest that the COX-2/NF-kappaB pathway may play a role in the pathogenesis of NEC. Therapeutic agents that target this pathway may prove useful in the treatment or possible prevention of NEC.
Chung
D H
DH
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555-0353, USA. dhchung@utmb.edu
Ethridge
R T
RT
Kim
S
S
Owens-Stovall
S
S
Hernandez
A
A
Kelly
D R
DR
Evers
B M
BM
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D020345:Enterocolitis, Necrotizing / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007421:Intestine, Small / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats
D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases