ESSENTIAL ROLE OF NUCLEAR FACTOR KAPPA-B IN THE INDUCTION OF EOSINOPHILIA IN ALLERGIC AIRWAY INFLAMMATION

The molecular mechanisms that contribute to an eosinophil-rich airway inflammation in asthma are unclear. A predominantly T helper 2 (Th2)-t ype cell response has been documented in allergic asthma. Here we show that mice deficient in the p50 subunit of nuclear factor (NF)-kappa B are incapable of mounting eosinophilic airway inflammation compared w ith wild-type mice. This deficiency was not due to a block in T cell p riming or proliferation in the p50(-/-) mice, nor was it due to a defe ct in the expression of the cell adhesion molecules VCAM-1 and ICAM-1 that are required for the extravasation of eosinophils into the airway s. The major defects in the p50(-/-) mice were the lack of production of the Th2 cytokine interleukin 5 and the chemokine eotaxin, which are crucial for proliferation and for differentiation and recruitment, re spectively, of eosinophils into the asthmatic airway. Additionally, th e p50(-/-) mice were deficient in the production of the chemokines mac rophage inflammatory protein (MIP)-1 alpha and MIP-1 beta that have be en implicated in T cell recruitment to sites of inflammation. These re sults demonstrate a crucial role for NF-kappa B in vivo in the express ion of important molecules that have been implicated in the pathogenes is of asthma.