Oxysterol represses high-affinity IgE receptor-stimulated mast cell activation in Liver X receptor-dependent and -independent manners.
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.
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.
Satoshi
S
Nunomura
Kaori
K
Endo
Makoto
M
Makishima
Chisei
C
Ra
D000818:Animals; D000915:Antibody Affinity / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D002777:Cholestanols / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006888:Hydroxycholesterols / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D000071518:Liver X Receptors; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D017455:Receptors, IgE / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013261:Sterols / Q000494:pharmacology*
D002777:Cholestanols; D006888:Hydroxycholesterols; D015850:Interleukin-6; C107473:LY 295427; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D017455:Receptors, IgE; D013261:Sterols; C007997:25-hydroxycholesterol