Oxysterol represses high-affinity IgE receptor-stimulated mast cell activation in Liver X receptor-dependent and -independent manners
Abstract
Oxysterols activating liver X receptors (LXRs) repress expression of pro-inflammatory genes and have anti-inflammatory effects. Here, we show for the first time that bone marrow-derived murine mast cells (BMMCs) predominantly express LXRβ. 25-hydroxycholesterol, a representative LXR activating oxysterol, suppressed IL-6 production and degranulation response in BMMCs following engagement of high-affinity IgE receptor (FcεRI). Interestingly, 25-hydroxycholesterol reduced cell-surface FcεRI expression by inhibiting assembly of FcεRIα and FcεRIβ. We demonstrate that LXR activation was involved in the suppression of IL-6 production in BMMCs, but that reduced FcεRI expression and degranulation response was mediated in an LXR-independent manner.
Abbreviations: BMMCs, bone marrow-derived mast cells, FcεRI, high-affinity IgE, LXR, liver X receptor, LDLR, LDL receptor, 25-OHC, 25-hydroxycholesterol, 22(R)-OHC, 22(R)-hydroxycholesterol, 24(S),25-EC, 24(S),25-epoxycholesterol, 22(S)-hydroxycholesterol, (22(S)-OHC), ER, endoplasmic reticulum, SREBP, sterol regulatory element-binding protein
Keywords: Mast cell, IgE receptor, Nuclear receptor, Cytokine production, Cell degranulation
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PII: S0014-5793(10)00100-6
doi:10.1016/j.febslet.2010.02.006
© 2010 Federation of European Biochemical Societies
