Activation of LXRs using the synthetic agonist GW3965 represses the production of pro-inflammatory cytokines by murine mast cells

Allergology International : Official Journal of the Japanese Society of Allergology
Satoshi NunomuraChisei Ra

Abstract

The activation of liver X receptor (LXR) α or LXRβ negatively regulates the expression of pro-inflammatory 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 MC-mediated production of pro-inflammatory cytokines, including IL-6, are poorly understood. Therefore, we employed the synthetic LXR ligand GW3965 to examine the functions of LXRα and LXRβ in the production of pro-inflammatory cytokines by murine bone marrow-derived MCs (BMMCs). We prepared BMMCs from wild-type (WT), LXRα(-/-), and LXRα/β(-/-) mice. Each group of BMMCs was pretreated with GW3965 and then stimulated with IgE+antigen (Ag) or lipopolysaccharide (LPS). Cytokine production was then analyzed using specific ELISA kits. The activation of LXRs by GW3965 significantly attenuated the production of IL-1α and IL-1β, but not of IL-6, in the WT and LXRα(-/-) BMMCs stimulated with IgE+Ag. However, GW3965 treatment decreased the production of IL-1α, IL-1β,...Continue Reading

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Citations

Jul 26, 2018·International Journal of Molecular Sciences·Sarah DallelSalwan Maqdasy
Nov 27, 2019·Cells·Ralf WeiskirchenMichael Huber
Aug 9, 2018·International Journal of Molecular Sciences·Adil Rasheed, Carolyn L Cummins
Dec 12, 2020·Journal of Cellular Physiology·Lin ZhaoYang Yang

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