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 LXRbeta. 25-hydroxycholesterol, a representative LXR activating oxysterol, suppressed IL-6 production and degranulation response in BMMCs following engagement of high-affinity IgE receptor (FcepsilonRI). Interestingly, 25-hydroxycholesterol reduced cell-surface FcepsilonRI expression by inhibiting assembly of FcepsilonRIalpha and FcepsilonRIbeta. We demonstrate that LXR activation was involved in the suppression of IL-6 production in BMMCs, but that reduced FcepsilonRI expression and degranulation response was mediated in an LXR-independent manner.