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

ABSTRACT: Liver X receptors (LXRs) have emerged as important regulators of inflammatory gene expression. Previously, we had reported that an LXR? gene promoter polymorphism (-1830 T?>?C) is associated with systemic lupus erythematosus (SLE). Therefore, we assessed cytokine expression in relation to LXR? 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 LXR? promoter constructs. Additionally, peripheral blood mononuclear cell- (PBMC-) derived macrophages from the patients were evaluated for proinflammatory cytokines in relation to the genotypes of LXR? -1830 T?>?C. The expression of LXR? was increased in macrophages; levels of proinflammatory cytokines were decreased with LXR? expression. Production of proinflammatory cytokines varied depending on LXR? -1830 T?>?C genotype. In particular, expression of LXR? was decreased and that of proinflammatory cytokines was increased for LXR? -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 LXR?, according to LXR? -1830 T?>?C genotype, may contribute to the inflammatory response by induction of inflammatory cytokines in SLE.

SUBMITTER: Kim HA 

PROVIDER: S-EPMC6421810 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature