| First Author | Park K | Year | 2010 |
| Journal | J Leukoc Biol | Volume | 88 |
| Issue | 6 | Pages | 1081-7 |
| PubMed ID | 20699362 | Mgi Jnum | J:166647 |
| Mgi Id | MGI:4848284 | Doi | 10.1189/jlb.0610318 |
| Citation | Park K, et al. (2010) Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons. J Leukoc Biol 88(6):1081-7 |
| abstractText | 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 IFNalphaR and JAK/STAT1 pathway. Treatment of BMDCs and macrophages with IFN-alpha or IFN-beta induces Ch25h in a STAT1-dependent manner. IFN-gamma 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 IFNalphaR 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. |
