TY - JOUR
T1 - Molecular mechanisms contributing to necrotizing enterocolitis
AU - Chung, Dai H.
AU - Ethridge, Richard T.
AU - Kim, Sunghoon
AU - Owens-Stovall, Sharla
AU - Hernandez, Ambrosio
AU - Kelly, David R.
AU - Evers, B. Mark
PY - 2001
Y1 - 2001
N2 - Objective To examine the cellular mechanisms involved in the pathogenesis of necrotizing enterocolitis (NEC). Summary Background Data 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)-κB 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 μg/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-κB 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-κB 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-κB binding was noted in a rodent model of NEC. These findings suggest that the COX-2/NF-κB 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.
AB - Objective To examine the cellular mechanisms involved in the pathogenesis of necrotizing enterocolitis (NEC). Summary Background Data 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)-κB 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 μg/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-κB 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-κB 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-κB binding was noted in a rodent model of NEC. These findings suggest that the COX-2/NF-κB 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.
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U2 - 10.1097/00000658-200106000-00014
DO - 10.1097/00000658-200106000-00014
M3 - Article
C2 - 11371742
AN - SCOPUS:0034988440
SN - 0003-4932
VL - 233
SP - 835
EP - 842
JO - Annals of Surgery
JF - Annals of Surgery
IS - 6
ER -