Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency

摘要: Stimulation with lipopolysaccharide (LPS; endotoxin) not only causes rapid production of proinflammatory cytokines, but also induces a state LPS hypo-responsiveness to second stimulation (endotoxin tolerance (ET)). Murine bone marrow-derived MCs (BMMCs) and peritoneal (PMCs) developed ET as shown by an abrogated Il6/Tnf RNAs IL-6/TNF-α proteins. In naive BMMCs, induced transient decline in the trimethylation lysine 9 core histone H3 (H3K9me3), suppressive chromatin mark, at promoters, which correlated p50(NFκB) p65(NFκB) binding. Both demethylation NFκB binding were tolerant cells. addition, cytosolic activation was suppressed BMMCs. Intriguingly, antigen comparable IL-6/TNF-α, although affected antigen-triggered NFκB; pharmacological analysis indicated importance Ca2+-dependent transcription this respect. macrophages, IκB member BCL3 is known be involved ET, corroborated comparing wild-type Bcl3-deficient Interestingly, PMCs produce markedly increased amounts after stimulation. Collectively, BCL3-independent, however, PMCs, negatively regulates immediate LPS-induced cytokine quantitatively affects ET.