RATIONALE: Injurious agents often cause less severe injury in neonates as compared with adults. OBJECTIVE: We hypothesized that maturational differences in lung inflammation induced by lipopolysaccharide (LPS) may be related to the nature of the nuclear factor (NF)-kappaB complex activated, and the profile of target genes expressed. METHODS: Neonatal and adult mice were injected with intraperitoneal LPS. Lung inflammation was assessed by histology, and apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase UTP nick-end labeling). The expression of candidate inflammatory and apoptotic mediators was evaluated by quantitative real-time polymerase chain reaction and Western immunoblot. RESULTS: Neonates demonstrated reduced inflammation and apoptosis, 24 hours after LPS exposure, as compared with adults. This difference was associated with persistent activation of NF-kappaB p65p50 heterodimers in the neonates in contrast to early, transient activation of p65p50 followed by sustained activation of p50p50 in the adults. Adults had increased expression of a panel of inflammatory and proapoptotic genes, and repression of antiapoptotic targets, whereas no significant changes in these mediators were observed in the neonates. Inhibition of NF-kappaB activity in the neonates decreased apoptosis, but heightened inflammation, with increased expression of the same inflammatory genes elevated in the adults. In contrast, inhibition of NF-kappaB in the adults resulted in partial suppression of the inflammatory response. CONCLUSIONS: NF-kappaB activation in the neonatal lung is antiinflammatory, protecting against LPS-mediated lung inflammation by repressing similar inflammatory genes induced in the adult.
RATIONALE: Injurious agents often cause less severe injury in neonates as compared with adults. OBJECTIVE: We hypothesized that maturational differences in lung inflammation induced by lipopolysaccharide (LPS) may be related to the nature of the nuclear factor (NF)-kappaB complex activated, and the profile of target genes expressed. METHODS: Neonatal and adult mice were injected with intraperitoneal LPS. Lung inflammation was assessed by histology, and apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase UTP nick-end labeling). The expression of candidate inflammatory and apoptotic mediators was evaluated by quantitative real-time polymerase chain reaction and Western immunoblot. RESULTS: Neonates demonstrated reduced inflammation and apoptosis, 24 hours after LPS exposure, as compared with adults. This difference was associated with persistent activation of NF-kappaB p65p50 heterodimers in the neonates in contrast to early, transient activation of p65p50 followed by sustained activation of p50p50 in the adults. Adults had increased expression of a panel of inflammatory and proapoptotic genes, and repression of antiapoptotic targets, whereas no significant changes in these mediators were observed in the neonates. Inhibition of NF-kappaB activity in the neonates decreased apoptosis, but heightened inflammation, with increased expression of the same inflammatory genes elevated in the adults. In contrast, inhibition of NF-kappaB in the adults resulted in partial suppression of the inflammatory response. CONCLUSIONS: NF-kappaB activation in the neonatal lung is antiinflammatory, protecting against LPS-mediated lung inflammation by repressing similar inflammatory genes induced in the adult.
Authors: Shuichi Fujioka; Christian Schmidt; Guido M Sclabas; Zhongkui Li; Hélène Pelicano; Bailu Peng; Alice Yao; Jiangong Niu; Wei Zhang; Douglas B Evans; James L Abbruzzese; Peng Huang; Paul J Chiao Journal: J Biol Chem Date: 2004-04-21 Impact factor: 5.157
Authors: Ian B Copland; Francisco Martinez; Brian P Kavanagh; Doreen Engelberts; Colin McKerlie; Jaques Belik; Martin Post Journal: Am J Respir Crit Care Med Date: 2004-01-07 Impact factor: 21.405
Authors: Jennifer M S Sucre; Kasey C Vickers; John T Benjamin; Erin J Plosa; Christopher S Jetter; Alissa Cutrone; Meaghan Ransom; Zachary Anderson; Quanhu Sheng; Benjamin A Fensterheim; Namasivayam Ambalavanan; Bryan Millis; Ethan Lee; Andries Zijlstra; Melanie Königshoff; Timothy S Blackwell; Susan H Guttentag Journal: Am J Respir Crit Care Med Date: 2020-05-15 Impact factor: 21.405
Authors: R Blair Dodson; Kyle N Powers; Jason Gien; Paul J Rozance; Gregory Seedorf; David Astling; Kenneth Jones; Timothy M Crombleholme; Steven H Abman; Cristina M Alvira Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-05-03 Impact factor: 5.464