FEBS Letters
Volume 584, Issue 6 , Pages 1143-1148, 19 March 2010

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

Edited by Beat Imhof

  • Satoshi Nunomura

      Affiliations

    • Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Japan
  • ,
  • Kaori Endo

      Affiliations

    • Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Japan
  • ,
  • Makoto Makishima

      Affiliations

    • Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Japan
  • ,
  • Chisei Ra

      Affiliations

    • Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Japan
    • Corresponding Author InformationCorresponding author. Address: Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchikami-cho Itabashi-ku, Tokyo 173-8610, Japan. Fax: +81 3 3972 8227.

Received 6 November 2009; received in revised form 8 January 2010; accepted 1 February 2010. published online 05 February 2010.

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

FEBS Letters
Volume 584, Issue 6 , Pages 1143-1148, 19 March 2010