چکیده (انگلیسی):

Background: The activation of liver X receptor (LXR) a or LXRb negatively regulates the expression of proinflammatory
genes in mammalian cells. We recently reported that 25-hydroxycholesterol, a representative
LXR-activating oxysterol, suppresses IL-6 production in mouse mast cells (MCs) following its
engagement of the high-affinity IgE receptor (FcεRI). This finding suggests that murine MCs express
functional LXRs; however, the mechanisms underlying the LXR-dependent repression of the MCmediated
production of pro-inflammatory cytokines, including IL-6, are poorly understood. Therefore,
we employed the synthetic LXR ligand GW3965 to examine the functions of LXRa and LXRb in the
production of pro-inflammatory cytokines by murine bone marrow-derived MCs (BMMCs).
Methods: We prepared BMMCs from wild-type (WT), LXRa

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, and LXRa/b

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mice. Each group of
BMMCs was pretreated with GW3965 and then stimulated with IgEþantigen (Ag) or lipopolysaccharide
(LPS). Cytokine production was then analyzed using specific ELISA kits.
Results: The activation of LXRs by GW3965 significantly attenuated the production of IL-1a and IL-1b, but
not of IL-6, in the WT and LXRa

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BMMCs stimulated with IgEþAg. However, GW3965 treatment
decreased the production of IL-1a, IL-1b, and IL-6 inWT and LXRa

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BMMCs upon stimulation with LPS,
while the GW3965-mediated suppression of cytokine production was nearly absent from the LXRa/b

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BMMCs.
Conclusions: These findings demonstrate, for the first time, that the activation of LXRs by GW3965 attenuates
the antigen- or LPS-induced production of pro-inflammatory cytokines, such as IL-1a and IL-1b,
in murine MCs and that LXRb plays an important role in the LXR-mediated repression of cytokine
production.