Molecular mechanisms contributing to necrotizing enterocolitis

Dai H. Chung, Richard T. Ethridge, Sunghoon Kim, Sharla Owens-Stovall, Ambrosio Hernandez, David R. Kelly, B. Mark Evers

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)835-842
Number of pages8
JournalAnnals of surgery
Volume233
Issue number6
DOIs
StatePublished - Jun 11 2001

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ASJC Scopus subject areas

  • Surgery

Cite this

Chung, D. H., Ethridge, R. T., Kim, S., Owens-Stovall, S., Hernandez, A., Kelly, D. R., & Evers, B. M. (2001). Molecular mechanisms contributing to necrotizing enterocolitis. Annals of surgery, 233(6), 835-842. https://doi.org/10.1097/00000658-200106000-00014