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• W2034649992 abstract "Necrotizing enterocolitis (NEC) is a major cause of morbidity and death in premature infants. NEC is associated with increased levels of pro-inflammatory cytokines in plasma and tissues that are regulated by the transcription factor nuclear factor-kappaB (NF-kappaB). It remains unknown, however, whether NF-kappaB mediates injury in neonatal NEC. We therefore examined the activation status of NF-kappaB perinatally in the small intestine and in a neonatal rat model of NEC. We found that intestinal NF-kappaB is strongly activated at birth and, in dam-fed newborn rats, is down-regulated within a day. In contrast, NF-kappaB remains strongly activated at both d 1 and d 2 in stressed animals, and this is accompanied by a significant decrease in the levels of the endogenous NF-kappaB inhibitor protein IkappaBalpha and IkappaBbeta at d 2. To determine the importance of elevated NF-kappaB activity in intestinal injury in NEC, we administered the NEMO-binding domain (NBD) peptide that selectively inhibits the critical upstream IkappaB kinase (IKK). NBD but not a control peptide decreased mortality and bowel injury in this model, supporting the hypothesis that bowel injury in NEC results from elevated NF-kappaB activity. Our findings therefore lead us to conclude that selective NF-kappaB inhibition represents a promising therapeutic strategy for NEC." @default.
• W2034649992 created "2016-06-24" @default.
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• W2034649992 date "2007-06-01" @default.
• W2034649992 modified "2023-10-05" @default.
• W2034649992 title "Inhibition of Nuclear Factor-κB Ameliorates Bowel Injury and Prolongs Survival in a Neonatal Rat Model of Necrotizing Enterocolitis" @default.
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• W2034649992 doi "https://doi.org/10.1203/pdr.0b013e3180534219" @default.
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