Oxysterol represses high-affinity IgE receptor-stimulated mast cell activation in Liver X receptor-dependent and -independent manners

Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.
FEBS letters (Impact Factor: 3.17). 02/2010; 584(6):1143-8. DOI: 10.1016/j.febslet.2010.02.006
Source: PubMed


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.

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Available from: Chisei Ra, Jul 17, 2014
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    • "As the key effector molecule of type I hypersensitivity, IgE is critical for allergic immune reaction and AHR [17]. Previous studies have demonstrated that Liver X receptors attenuate IgE expression in B cells [18] and high-affinity IgE receptor-stimulated mast cell activation [19]. In our study, OVA-specific IgE production was blocked by T0901317 in animal models of asthma. "
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    ABSTRACT: Recent studies suggest that homeostasis of lipid metabolism is crucial for the function of various immune cells. Oxygenated derivatives of cholesterol (oxysterols) are well-known regulators of lipid metabolism and have diverse functions, such as inhibition of cholesterol synthesis, efflux of intracellular cholesterol, synthesis of cholesterol esters, and activation of liver X receptors (LXRs). In this review, we introduce novel roles of the oxysterol receptors LXRs in the immune system, including regulation of inflammatory responses, T cell expansion, immunoglobulin production, and antitumor responses. We also discuss lipid-mediated signaling as a potential target for treatment of immune diseases.
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