Protection of Mice from Allergen-induced Asthma by Selenite PREVENTION OF EOSINOPHIL INFILTRATION BY INHIBITION OF NF-κB ACTIVATION*

The potential anti-inflammatory effect of sodium selenite in a mouse model of asthma was investigated. Selenite was injected into the peritoneum of allergen (ovalbumin)-sensitized mice before allergen challenge. Ovalbumin challenge resulted in activation of the transcription factor NF-kappaB and an increase in the expression of cell adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, which are encoded by NF-kappaB-dependent genes) in lung tissue as well as in the recruitment of eosinophils to lung airways. These effects of ovalbumin challenge were all inhibited by pretreatment of mice with selenite. Selenite administration also increased the activity of selenium-dependent glutathione peroxidase in lung tissue. Furthermore, supplementation of A549 human airway epithelial cell cultures with selenite increased glutathione peroxidase activity as well as inhibited both the generation of hydrogen peroxide and the activation of NF-kappaB induced by tumor necrosis factor alpha in these cells. Selenite also reversed in vitro the activation of NF-kappaB induced by this cytokine in intact A549 cells. These results suggest that selenite regulates the activity of NF-kappaB by increasing the activity of glutathione peroxidase, thereby removing potential activators of NF-kappaB, and possibly also by direct oxidation of critical sulfhydryl groups of this transcription factor. These effects of selenite likely underlie its anti-inflammatory action in asthma.