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

Abstract

Listen

Translate article

Background: The transcription factor nuclear factor-κB (NF-κB) 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-κB in the regulation of allergic inflammation. Methods: To determine whether NF-κB is activated during IgE-mediated reactions and what types of mediators it regulates, a mutant form of IκB was used to block the ability of NF-κB 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-κB as assessed by electrophoretic mobility shift assays. Transfected mast cells expressing the mutant IκB showed very little NF-κB activation. Both control and transfected cells released β-hexosaminidase after specific antigen challenge, and this release could be potentiated by exogenous adenosine. Transfected mast cells that failed to develop NF-κB 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-κB activity. Conclusions: It appears that NF-κB 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-κB to reduce inflammatory processes, it is important to know precisely which cytokines are under its control. (J Allergy Clin Immunol 2000;105:500-5.)