Document Detail


NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness.
MedLine Citation:
PMID:  15557197     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Airways display robust NF-kappaB activation and represent targets for anti-inflammatory asthma therapies, but the functional importance of NF-kappaB activation in airway epithelium remains enigmatic. Therefore, transgenic mice were created in which NF-kappaB activation is repressed specifically in airways (CC10-IkappaBalpha(SR) mice). In response to inhaled Ag, transgenic mice demonstrated significantly ameliorated inflammation, reduced levels of chemokines, T cell cytokines, mucus cell metaplasia, and circulating IgE compared with littermate controls. Despite these findings, Ag-driven airways hyperresponsiveness was not attenuated in CC10-IkappaBalpha(SR) mice. This study clearly demonstrates that airway epithelial NF-kappaB activation orchestrates Ag-induced inflammation and subsequent adaptive immune responses, but does not contribute to airways hyperresponsiveness, the cardinal feature that underlies asthma.
Authors:
Matthew E Poynter; Roy Cloots; Tiest van Woerkom; Kelly J Butnor; Pamela Vacek; Douglas J Taatjes; Charles G Irvin; Yvonne M W Janssen-Heininger
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  173     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-23     Completed Date:  2005-01-14     Revised Date:  2010-09-20    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7003-9     Citation Subset:  AIM; IM    
Affiliation:
Vermont Lung Center and the Department of Medicine, Division of Pulmonary and Critical Care, University of Vermont, Burlington, VT 05405, USA.
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MeSH Terms
Descriptor/Qualifier:
Allergens / administration & dosage,  immunology
Animals
Antibody Specificity / genetics
Bronchial Hyperreactivity / genetics,  immunology*,  pathology*
Chemokines / antagonists & inhibitors,  biosynthesis
Cytokines / antagonists & inhibitors,  biosynthesis
I-kappa B Proteins / genetics
Immunoglobulin E / biosynthesis
Inflammation / genetics,  immunology,  prevention & control
Inflammation Mediators / antagonists & inhibitors,  metabolism,  physiology*
Lung / immunology,  metabolism*,  pathology*
Mice
Mice, Inbred BALB C
Mice, Transgenic
Mucus / secretion
NF-kappa B / antagonists & inhibitors,  metabolism,  physiology*
Ovalbumin / administration & dosage,  immunology
Respiratory Hypersensitivity / genetics,  immunology*,  pathology*,  prevention & control
Respiratory Mucosa / immunology,  metabolism,  pathology
T-Lymphocyte Subsets / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
1 P20 RR16462/RR/NCRR NIH HHS; K22 ES011652/ES/NIEHS NIH HHS; P01-HL-67004/HL/NHLBI NIH HHS; P20 RR015557-010002/RR/NCRR NIH HHS; P20 RR15557/RR/NCRR NIH HHS; R01 HL060014-01A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Allergens; 0/Chemokines; 0/Cytokines; 0/I-kappa B Proteins; 0/Inflammation Mediators; 0/NF-kappa B; 139874-52-5/NF-kappaB inhibitor alpha; 37341-29-0/Immunoglobulin E; 9006-59-1/Ovalbumin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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