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  • Title: Dependence of mast cell IgE-mediated cytokine production on nuclear factor-kappaB activity.
    Author: Marquardt DL, Walker LL.
    Journal: J Allergy Clin Immunol; 2000 Mar; 105(3):500-5. PubMed ID: 10719300.
    Abstract:
    BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) 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-kappaB in the regulation of allergic inflammation. METHODS: To determine whether NF-kappaB is activated during IgE-mediated reactions and what types of mediators it regulates, a mutant form of IkappaB was used to block the ability of NF-kappaB 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-kappaB as assessed by electrophoretic mobility shift assays. Transfected mast cells expressing the mutant IkappaB showed very little NF-kappaB 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-kappaB 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-kappaB activity. CONCLUSIONS: It appears that NF-kappaB 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-kappaB to reduce inflammatory processes, it is important to know precisely which cytokines are under its control.
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