LAUSR

Hyperoxia-induced acute lung injury (HALI) during mechanical ventilation can lead to excessive proinflammatory responses, endothelial and epithelial cell damage, and alveolar edema. We and others have demonstrated that NF-kB activation has a protective effect on cultured lung epithelial cells. The present study investigates the effects of NF-kB activation on ALI using CC10-I- κBαSR transgenic mice that are deficient in the NF-kB activation in airway epithelial cells. These mice showed significantly more severe lung injury than wild type mice after being exposed to 95% oxygen for 3 d, characterized by higher wet/dry weight ratios of lung tissue and increased total protein content in bronchoalveolar lavage fluids (BALF). Severe lung injury was associated with elevated neutrophil infiltration and extracellular HMGB1 accumulation in BALF. In addition, prolonged exposure of cultured human bronchial epithelial (HBE) cells to hyperoxia induced the release of HMGB1. Higher levels of extracellular HMGB1 were observed in HBE cells cultured with BAY 11–7082, an inhibitor of NF- kB activation. These results indicate that the NF-kB signaling pathway in airway epithelial cells plays an important protective role against HMGB1-mediated hyperoxic inflammatory lung injury.