Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons

Kiwon Park, Alan L. Scott

Research output: Contribution to journalArticlepeer-review

Abstract

The oxysterol-producing enzyme CH25H plays an important role in regulating lipid metabolism, gene expression, and immune activation. In vitro experiments using a panel of TLR agonists to activate BMDCs and macrophages demonstrated that Ch25h expression is induced rapidly, selectively, and robustly by the TLR ligands poly I:C and LPS. The mechanism of TLR3- and TLR4-induced transcription levels of Ch25h relies on the TRIF-mediated production of type I IFNs and requires signaling through the IFNαR and JAK/STAT1 pathway. Treatment of BMDCs and macrophages with IFN-α or IFN-β induces Ch25h in a STAT1-dependent manner. IFN-γ also up-regulated Ch25h expression by signaling through STAT1, suggesting that multiple pathways regulate the production of this enzyme. In addition, we demonstrated that regulation of Ch25h expression in vivo in lung-derived DCs and macrophages is dependent on signaling through the IFNαR and STAT1. The results suggest that the rapid induction of Ch25h and subsequent oxysterol synthesis may represent a component of the regulatory network that modulates the magnitude of innate immune reactions and possibly the nature and intensity of subsequent adaptive responses.

Original languageEnglish (US)
Pages (from-to)1081-1087
Number of pages7
JournalJournal of Leukocyte Biology
Volume88
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • Innate immunity
  • LPS
  • Lung
  • Poly I:C
  • STAT1
  • TLR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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