title: Heat shock pretreatment reduces intestinal injury in a neonatal rat model of early necrotizing enterocolitis.
abstract: BACKGROUND
  Increased pro-inflammatory cytokines are suggested in the pathogenesis of necrotizing enterocolitis (NEC). The transcription factor, nuclear factor-ĸB (NF-ĸB), is a central regulator of inflammatory and immune responses, and recent rodent NEC models have shown that NF-ĸB may have a critical role in the disease processes that underlie NEC. Heat shock proteins have important functions in response to stress-related events in a variety of systems, including digestive organs.
  
  
  OBJECTIVE
  We investigated whether heat shock pretreatment protects intestinal epithelial damage in the early NEC rat model.
  
  
  METHODS
  We generated human NEC-like lesions in neonatal rat ileum by administering oral endotoxin (10 mg/kg), intermittent 8% hypoxia, and hypertonic formula. Heat shock was administered by raising the chamber temperature to 42°C for 20 min, 3 h prior to endotoxin ingestion.
  
  
  RESULTS
  Heat shock pretreatment increased the expression of HSP70 in the ileal tissue and attenuated histological severity of early experimental NEC. NF-ĸB was activated in the ileal tissue of the NEC group and this activation was attenuated by heat shock pretreatment, which was determined by electrophoretic mobility shift assay and Western blot analysis of p50 in subcellular fractionated samples.
  
  
  CONCLUSIONS
  Heat shock pretreatment reduced the incidence and severity of early experimental NEC in rats. A possible mechanism underlying this protective effect includes inhibition of NF-ĸB activation through increased HSP70 expression.
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ee-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Kyeung-Yeup
authors.initials: KY
authors.lastname: Lee
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jin A
authors.initials: JA
authors.lastname: Lee
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Choi
authors.forename: Han-Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Beyong Il
authors.initials: BI
authors.lastname: Kim
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Choi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006979:Hyperthermia, Induced / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000293:injuries* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B