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- Title
NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer.
- Authors
Kisseleva, Tatiana; Li Song; Vorontchikhina, Marina; Feirt, Nikki; Kitajewski, Jan; Schindler, Christian
- Abstract
The transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-?B in endothelial tissues, Tie2 promoter/enhancer—IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress.
- Subjects
NF-kappa B; INFLAMMATION; HOMEOSTASIS; PHENOTYPES; APOPTOSIS; TUMORS
- Publication
Journal of Clinical Investigation, 2006, Vol 116, Issue 11, p2955
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI27392