The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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27-Hydroxycholesterol induces macrophage gene expression via LXR-dependent and -independent mechanisms

  • Kim, Bo-Young (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Son, Yonghae (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Cho, Hyok-rae (Department of Neurosurgery, Kosin University College of Medicine) ;
  • Lee, Dongjun (Department of Convergence Medicine, School of Medicine, Pusan National University) ;
  • Eo, Seong-Kug (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Kim, Koanhoi (Department of Pharmacology, School of Medicine, Pusan National University)
  • Received : 2020.06.09
  • Accepted : 2020.12.22
  • Published : 2021.03.01
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Abstract

27-Hydroxycholesterol (27OHChol) exhibits agonistic activity for liver X receptors (LXRs). To determine roles of the LXR agonistic activity in macrophage gene expression, we investigated the effects of LXR inhibition on the 27OHChol-induced genes. Treatment of human THP-1 cells with GSK 2033, a potent cell-active LXR antagonist, results in complete inhibition in the transcription of LXR target genes (such as LXRα and ABCA1) induced by 27OHChol or a synthetic LXR ligand TO 901317. Whereas expression of CCL2 and CCL4 remains unaffected by GSK 2033, TNF-α expression is further induced and 27OHChol-induced CCL3 and CXCL8 genes are suppressed at both the transcriptional and protein translation levels in the presence of GSK 2033. This LXR antagonist downregulates transcript levels and surface expression of CD163 and CD206 and suppresses the transcription of CD14, CD80, and CD86 genes without downregulating their surface levels. GSK 2033 alone had no effect on the basal expression levels of the aforementioned genes. Collectively, these results indicate that LXR inhibition leads to differential regulation of 27-hydroxycholesterol-induced genes in macrophages. We propose that 27OHChol induces gene expression and modulates macrophage functions via LXR-dependent and -independent mechanisms.

Keywords

References

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