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Selective blockade of NF-kappa B activity in airway immune cells inhibits the effector phase of experimental asthma.

Authors :
Desmet C
Gosset P
Pajak B
Cataldo D
Bentires-Alj M
Lekeux P
Bureau F
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Nov 01; Vol. 173 (9), pp. 5766-75.
Publication Year :
2004

Abstract

Knockout mice studies have revealed that NF-kappaB plays a critical role in Th2 cell differentiation and is therefore required for induction of allergic airway inflammation. However, the questions of whether NF-kappaB also plays a role in the effector phase of airway allergy and whether inhibiting NF-kappaB could have therapeutic value in the treatment of established asthma remain unanswered. To address these issues, we have assessed in OVA-sensitized wild-type mice the effects of selectively antagonizing NF-kappaB activity in the lungs during OVA challenge. Intratracheal administration of NF-kappaB decoy oligodeoxynucleotides to OVA-sensitized mice led to efficient nuclear transfection of airway immune cells, but not constitutive lung cells and draining lymph node cells, associated with abrogation of NF-kappaB activity in the airways upon OVA provocation. NF-kappaB inhibition was associated with strong attenuation of allergic lung inflammation, airway hyperresponsiveness, and local production of mucus, IL-5, IL-13, and eotaxin. IL-4 and OVA-specific IgE and IgG1 production was not reduced. This study demonstrates for the first time that activation of NF-kappaB in local immune cells is critically involved in the effector phase of allergic airway disease and that specific NF-kappaB inhibition in the lungs has therapeutic potential in the control of pulmonary allergy.

Details

Language :
English
ISSN :
0022-1767
Volume :
173
Issue :
9
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
15494529
Full Text :
https://doi.org/10.4049/jimmunol.173.9.5766