Reference : Selective blockade of NF-kappa B activity in airway immune cells inhibits the effecto...
Scientific journals : Article
Life sciences : Veterinary medicine & animal health
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
Selective blockade of NF-kappa B activity in airway immune cells inhibits the effector phase of experimental asthma
Desmet, Christophe [Université de Liège - ULiège > > Biochimie et biologie moléculaire >]
Gosset, P. [> > > >]
Pajak, B. [> > > >]
Cataldo, Didier mailto [Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques]
Bentires-Alj, M. [> > > >]
Lekeux, Pierre mailto [Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie >]
Bureau, Fabrice mailto [Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie et biologie moléculaire >]
Journal of Immunology
Amer Assoc Immunologists
Yes (verified by ORBi)
[en] 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
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