NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer

The transcription factor NF-kappa B is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-kappa B, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-kappa B in endothelial tissues, Tie2 promoter/enhancer-I kappa B alpha(S32A/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-kappa B 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-kappa B plays an important role in the maintenance of vascular integrity and response to stress.