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Selective blockade of NF-kappa B activity in airway immune cells inhibits the effector phase of experimental asthma.
- 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.
- Subjects :
- Allergens administration & dosage
Allergens immunology
Animals
Apoptosis drug effects
Apoptosis immunology
Asthma pathology
Bronchial Hyperreactivity immunology
Bronchial Hyperreactivity metabolism
Bronchial Hyperreactivity pathology
Chemokine CCL11
Chemokines, CC antagonists & inhibitors
Chemokines, CC biosynthesis
Female
Immunoglobulins biosynthesis
Interleukin-13 antagonists & inhibitors
Interleukin-13 biosynthesis
Interleukin-4 biosynthesis
Interleukin-5 antagonists & inhibitors
Interleukin-5 biosynthesis
Intubation, Intratracheal
Lung pathology
Lymph Nodes immunology
Lymph Nodes metabolism
Lymph Nodes pathology
Mice
Mice, Inbred BALB C
Mucus metabolism
NF-kappa B administration & dosage
Oligodeoxyribonucleotides, Antisense administration & dosage
Oligodeoxyribonucleotides, Antisense metabolism
Ovalbumin administration & dosage
Ovalbumin immunology
Respiratory Mucosa pathology
Th2 Cells immunology
Th2 Cells metabolism
Thorax
Asthma immunology
Asthma metabolism
Lung immunology
Lung metabolism
NF-kappa B antagonists & inhibitors
NF-kappa B metabolism
Respiratory Mucosa immunology
Respiratory Mucosa metabolism
Subjects
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