title: Essential role of nuclear factor kappaB in the induction of eosinophilia in allergic airway inflammation.
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)- kappaB 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)-1alpha and MIP-1beta that have been implicated in T cell recruitment to sites of inflammation. These results demonstrate a crucial role for NF-kappaB in vivo in the expression of important molecules that have been implicated in the pathogenesis of asthma.
authors.affiliation: Department of Internal Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Cohn
authors.forename: D H
authors.initials: DH
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Homer
authors.forename: A
authors.initials: A
authors.lastname: Ray
authors.forename: P
authors.initials: P
authors.lastname: Ray
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004802:Eosinophilia / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D052002:NF-kappa B p50 Subunit; D010047:Ovalbumin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000941:Antigens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D017931:DNA Primers; D015848:Interleukin-5; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D010047:Ovalbumin