The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

Abstract EN

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 from patients with SLE.

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, peripheral blood mononuclear cell- (PBMC-) derived macrophages from the patients were evaluated for proinflammatory cytokines in relation to the genotypes of LXRα -1830 T > C.

The expression of LXRα was increased in macrophages; levels of proinflammatory cytokines were decreased with LXRα expression.

Production of proinflammatory cytokines varied depending on LXRα -1830 T > C genotype.

In particular, expression of LXRα was decreased and that of proinflammatory cytokines was increased for LXRα -1830 TC genotype compared to that for TT genotype.

The data were consistent in PBMC-derived macrophages from patients with SLE.

Increased proinflammatory cytokines is related to TLR7 and TLR9 expression.

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