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118 The liver x receptor is highly upregulated in monocyte derived macrophage and potentiates tlr-driven cytokine release according to genotype of -1830 t > c polymorphism
  1. CH Suh1,
  2. HA Kim1,
  3. WY Baek1,
  4. JY Jung1,
  5. SH Lee2 and
  6. SS Kim3
  1. 1Ajou University School of Medicine, Rheumatology, Suwon, Republic of Korea
  2. 2Konkouk University Medical Centre, Rheumatology, Seoul, Republic of Korea
  3. 3Ulsan University College of Medicine, Rheumatology, Gangneung, Republic of Korea

Abstract

Background and aims Liver X receptors (LXRs) are originally identified as ligand-dependent transcriptional activators and induce target genes involved in lipid metabolism. Also, LXRs have emerged as important regulators of inflammatory gene expression in several diseases. We previously reported that LXRα gene (NR1H3) promoter polymorphism (−1830 T > C) are associated with systemic lupus erythematosus (SLE) in Koreans. Therefore, we assessed cytokine expressions according to the LXRa polymorphism in monocyte-derived macrophages from SLE patients.

Methods Macrophages were obtained after 72 hour of culture of human monocytes (U937 and THP-1) supplemented with PMA (80 nM). Cells were transfected with LXRα promoter constructs. Supernatants were evaluated by enzyme-linked immunosorbent assay for proinflammatory cytokines. Also, peripheral blood mononuclear cells (PBMCs)-derived macrophages from SLE patients were evaluated for proinflammatory cytokines according to genotypes of LXRα −1830T>C.

Results The expression of LXRα is increased in human monocyte-derived macrophages. Proinflammatory cytokines, such as IL-1β and TNF-α are decreased in expression of LXRα. Production of proinflammatory cytokines are different according to expression of genotypes of LXRα −1830T>C. Especially, expression of LXRα is decreased and proinflammatory cytokines are increased in TC type of LXRα −1830T>C compared to TT type. These data are consistent in human PBMC-derived macrophages from SLE patients according to genotypes. Increased expression of proinflammatory cytokines is related to TLR7 and TLR9 expression with LXRα.

Conclusions These data suggest that expression of LXRα according to genotypes of LXRα −1830T>C may contribute to the inflammatory response by induction of inflammatory cytokines in SLE.

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