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Oxysterol represses high-affinity IgE receptor-stimulated mast cell activation in Liver X receptor-dependent and -independent manners
Authors:Satoshi Nunomura  Makoto Makishima
Affiliation:a Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Japan
b Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Japan
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.
Keywords: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
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