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

• DOI: 10.1189/jlb.0610318
• Publication Date: 2010-08-11T03:47:26Z
• Authors: Kiwon Park; Alan L Scott
• Keywords: Oxysterol; TRIF; STAT1; TLR3

Abstract TLR-mediated induction of cholesterol 25-hydoxylase transcription in dendritic cells and macrophages is dependent on IFN-α/IFN-β signaling through INF-αR STAT1. The oxysterol-producing enzyme CH25H plays an important role regulating lipid metabolism, gene expression, immune activation. In vitro experiments using a panel TLR agonists to activate BMDCs demonstrated that Ch25h expression induced rapidly, selectively, robustly by the ligands poly I:C LPS. mechanism TLR3- TLR4-induced levels relies TRIF-mediated production type I IFNs requires IFNαR JAK/STAT1 pathway. Treatment with IFN-α or IFN-β induces STAT1-dependent manner. IFN-γ also up-regulated STAT1, suggesting multiple pathways regulate this enzyme. addition, we regulation vivo lung-derived DCs results suggest rapid subsequent oxysterol synthesis may represent component regulatory network modulates magnitude innate reactions possibly nature intensity adaptive responses.