Format

Send to

Choose Destination
Eur J Immunol. 2007 Sep;37(9):2509-17.

NF-kappaB p50 and p65 subunits control intestinal homeostasis.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Abstract

Mice which lack the p50 subunit of NF-kappaB and are heterozygous for the p65 subunit (3X mice), are exquisitely sensitive to LPS-induced shock. Here, we demonstrate that prior to becoming moribund, 3X mice challenged with LPS develop a profound enteropathy. The enteropathy is characterized by defects in intestinal barrier function, increased epithelial apoptosis, and deregulated intestinal cytokine gene expression. The defect that sensitizes 3X mice to LPS-induced enteropathy is located within the innate immune compartment, as LPS induced similar findings in 3X mice lacking lymphocytes (3X/RAG). TNF-alpha depletion ameliorated the ability of LPS to induce pathology and TNF-alpha was able to independently induce similar findings, suggesting that TNF-alpha plays a critical role in the development of LPS-induced pathology in these mice. These data highlight that NF-kappaB subunits have essential functions in regulating intestinal homeostasis during acute inflammation.

PMID:
17705134
DOI:
10.1002/eji.200737186
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center