Background/Purpose: Liver X receptors (LXRs) have emerged as important regulators of inflammatory gene expression. Previously, we had reported that an LXRα gene promoter polymorphism (-1830 T>C) is associated with systemic lupus erythematosus (SLE). Therefore, we assessed cytokine expression in relation to LXRα polymorphism in monocyte-derived macrophages and peripheral blood mononuclear cells (PBMC) from patients with SLE.

Methods: Macrophages were obtained after 72 hours of culture of human monocytes supplemented with phorbol 12-myristate 13-acetate. Cells were transfected with LXRα promoter constructs. Additionally, PBMC-derived macrophages from the patients with SLE were evaluated for pro-inflammatory cytokines in relation to the genotypes of LXRα -1830 T>C.

Results: The expression of LXRα was increased in macrophages; levels of pro-inflammatory cytokines, such as IL-1β and TNF-α, were decreased with increased expression of LXRα. Production of pro-inflammatory cytokines varied depending on the expression of LXRα -1830 T>C genotype. In particular, decreased LXRα expression with increased pro-inflammatory cytokine expression was observed in monocyte-derived macrophages transfected with the TC genotype of LXRα -1830 T>C compared to those in cells transfected with the TT genotype. To verify the involvement of TLR in the expression of pro-inflammatory cytokines according to LXRα -1830 T>C genotype, various TLR agonists were treated in monocyte-derived macrophages transfected with the LXRα -1830 T>C. The levels of pro-inflammatory cytokines were further increased in TC genotype-transfected cells compared to those in TT genotype-transfected cells with treatment of TLR7 and TLR9 agonist. Pro-inflammatory cytokine levels were significantly decreased in TC genotype-transfected cells after treatment with TLR7 or TLR9 inhibitors. These results are consistent with those of an ex vivo study on PBMCs from patients with SLE with respect to the TC and TT genotypes of LXRα -1830.

Conclusion: These data suggest that expression levels of LXRα, according to LXRα -1830 T>C genotype, may contribute to the inflammatory response by induction of inflammatory cytokines in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-liver-x-receptor-modulates-inflammatory-cytokines-based-on-lxr%ce%b1-polymorphism-in-monocyte-derived-macrophages-and-patients-with-systemic-lupus-erythematosus/