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Nuclear factor-kappaB activation in neonatal mouse lung protects against lipopolysaccharide-induced inflammation.


ABSTRACT:

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.

SUBMITTER: Alvira CM 

PROVIDER: S-EPMC1899293 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Publications

Nuclear factor-kappaB activation in neonatal mouse lung protects against lipopolysaccharide-induced inflammation.

Alvira Cristina M CM   Abate Aida A   Yang Guang G   Dennery Phyllis A PA   Rabinovitch Marlene M  

American journal of respiratory and critical care medicine 20070125 8


<h4>Rationale</h4>Injurious agents often cause less severe injury in neonates as compared with adults.<h4>Objective</h4>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.<h4>Methods</h4>Neonatal and adult mice were injected with intraperitoneal LPS. Lung inflammation was assessed by histology, and apoptosis was determined  ...[more]

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