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B Activity in Airway Immune Cells Inhibits the Effector Phase of Experimental Asthma1
Laboratoires de
*
Physiologie,
Service de Pneumologie, and
Chimie Médicale, Centre de Thérapie Cellulaire et Moléculaire, Université de Liège, Liège, Belgium;
Institut National de la Santé et de la Recherche Médicale, Unité 416, Institut Pasteur de Lille, Lille, France; and
¶ Laboratoire de Physiologie Animale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium
Knockout mice studies have revealed that NF-
B plays a critical role in Th2 cell differentiation and is therefore required for induction of allergic airway inflammation. However, the questions of whether NF-B also plays a role in the effector phase of airway allergy and whether inhibiting NF-B 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-B activity in the lungs during OVA challenge. Intratracheal administration of NF-B 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-B activity in the airways upon OVA provocation. NF-B 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-B in local immune cells is critically involved in the effector phase of allergic airway disease and that specific NF-B inhibition in the lungs has therapeutic potential in the control of pulmonary allergy.
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