Dependence of mast cell IgE-mediated cytokine production on nuclear factor-kappaB activity.
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.
Marquardt
D L
DL
Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, Calif, USA.
Walker
L L
LL
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015550:Cell Degranulation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004586:Electrophoresis; D007073:Immunoglobulin E / Q000494:pharmacology; D015847:Interleukin-4; D015848:Interleukin-5; D015850:Interleukin-6 / Q000235:genetics; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D003432:Cross-Linking Reagents; D016207:Cytokines; D015848:Interleukin-5; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E