Dependence of mast cell IgE-mediated cytokine production on nuclear factor-kappa B activity

Background: The transcription factor nuclear factor-kappa B (NF-kappa B) has been implicated in the regulation of a number of inflammatory cytokines and has been the proposed target for anti-inflammatory therapeutics, Objective: Our purpose was to explore the role of NF-kappa B in the regulation of allergic inflammation. Methods: To determine whether NF-kappa B is activated during IgE-mediated reactions and what types of mediators it regulates, a mutant form of I kappa B was used to block the ability of NF-kappa B to translocate to the nucleus and promote the transcription of selected genes, Results: Mouse bone marrow-derived mast cells stimulated by IgE receptor cross-linking exhibited an activation of NF-kappa B as assessed by electrophoretic mobility shift assays. Transfected mast cells expressing the mutant I kappa B showed very little NF-kappa B activation, Both control and transfected cells released beta-hexosaminidase after specific antigen challenge, and this release could be potentiated by exogenous adenosine, Transfected mast cells that failed to develop NF-kappa B activation did not produce IL-6 messenger RNA or protein after IgE-mediated stimulation, but these cells retained the ability to produce transcripts for IL-4 and IL-5 in spite of the suppression of NF-kappa B activity. Conclusions: It appears that NF-kappa B is activated during IgE-mediated allergic inflammation and that this activity is necessary for the production of IL-6, but not IL-4 or IL-5. When considering the use of agents that target NF-kappa B to reduce inflammatory processes, it is important to know precisely which cytokines are under its control.