Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation |
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Authors: | Liyan Yang Lauren Cohn Dong-Hong Zhang Robert Homer Anuradha Ray Prabir Ray |
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Affiliation: | From the *Department of Internal Medicine, Pulmonary and Critical Care Section, the ‡Section of Immunobiology, and the §Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520 |
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Abstract: | The molecular mechanisms that contribute to an eosinophil-rich airway inflammation in asthma are unclear. A predominantly T helper 2 (Th2)-type cell response has been documented in allergic asthma. Here we show that mice deficient in the p50 subunit of nuclear factor (NF)- κB are incapable of mounting eosinophilic airway inflammation compared with wild-type mice. This deficiency was not due to a block in T cell priming or proliferation in the p50−/− mice, nor was it due to a defect in the expression of the cell adhesion molecules VCAM-1 and ICAM-1 that are required for the extravasation of eosinophils into the airways. 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, respectively, of eosinophils into the asthmatic airway. Additionally, the p50−/− mice were deficient in the production of the chemokines macrophage inflammatory protein (MIP)-1α and MIP-1β that have been implicated in T cell recruitment to sites of inflammation. These results demonstrate a crucial role for NF-κB in vivo in the expression of important molecules that have been implicated in the pathogenesis of asthma. |
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Keywords: | allergic inflammation, eosinophils, nuclear factor κ B, interleukin 5, eotaxin |
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