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Essential role of nuclear factor kappaB in the induction of eosinophilia in allergic airway inflammation.
- Source :
-
The Journal of experimental medicine [J Exp Med] 1998 Nov 02; Vol. 188 (9), pp. 1739-50. - Publication Year :
- 1998
-
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.
- Subjects :
- Animals
Antigens administration & dosage
Asthma immunology
Asthma pathology
Base Sequence
Chemokine CCL11
Cytokines biosynthesis
DNA Primers genetics
Eosinophilia immunology
Eosinophilia pathology
Gene Expression
Inflammation immunology
Inflammation pathology
Intercellular Adhesion Molecule-1 biosynthesis
Interleukin-4 biosynthesis
Interleukin-4 genetics
Interleukin-5 biosynthesis
Interleukin-5 genetics
Lung immunology
Lung pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B deficiency
NF-kappa B genetics
NF-kappa B p50 Subunit
Ovalbumin immunology
Reverse Transcriptase Polymerase Chain Reaction
Th2 Cells immunology
Vascular Cell Adhesion Molecule-1 biosynthesis
Asthma etiology
Chemokines, CC
Eosinophilia etiology
Inflammation etiology
NF-kappa B immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 188
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 9802985
- Full Text :
- https://doi.org/10.1084/jem.188.9.1739