The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response
Open accessAbstract
Recent studies suggest that the sterol metabolic network participates in the interferon (IFN) antiviral response. However, the molecular mechanisms linking IFN with the sterol network and the identity of sterol mediators remain unknown. Here we report a cellular antiviral role for macrophage production of 25-hydroxycholesterol (cholest-5-en-3β,25-diol, 25HC) as a component of the sterol metabolic network linked to the IFN response via Stat1. By utilizing quantitative metabolome profiling of all naturally occurring oxysterols upon infection or IFN-stimulation, we reveal 25HC as the only macrophage-synthesized and -secreted oxysterol. We show that 25HC can act at multiple levels as a potent paracrine inhibitor of viral infection for a broad range of viruses. We also demonstrate, using transcriptional regulatory-network analyses, genetic interventions and chromatin immunoprecipitation experiments that Stat1 directly coupled Ch25h regulation to IFN in macrophages. Our studies describe a physiological role for 25HC as a sterol-lipid effector of an innate immune pathway.
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Cites
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Statins as a newly recognized type of immunomodulator.
Kwak, B., Mulhaupt, F., Myit, S., & Mach, F. (2000) · Nature Medicine · doi:10.1038/82219 · Cited by 1,383
Bauman, D. R., Bitmansour, A. D., McDonald, J. G., Thompson, B. M., Liang, G., & Russell, D. W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909142106 · Cited by 329
Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide
Diczfalusy, U., Olofsson, K. E., Carlsson, A.-M., Gong, M., Golenbock, D. T., Rooyackers, O., Fläring, U., & Björkbacka, H. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m900107-jlr200 · Cited by 204
Cited by
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067
Interferon-Stimulated Genes: What Do They All Do?
Schoggins, J. W. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015756 · Cited by 1,036
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
York, A. G., Williams, K. J., Argus, J. P., Zhou, Q. D., Brar, G., Vergnes, L., Gray, E. E., Zhen, A., Wu, N. C., Yamada, D. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.045 · Cited by 461
25-Hydroxycholesterol suppresses interleukin-1–driven inflammation downstream of type I interferon
Reboldi, A., Dang, E. V., McDonald, J. G., Liang, G., Russell, D. W., & Cyster, J. G. (2014) · Science · doi:10.1126/science.1254790 · Cited by 444
Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation
Dang, E. V., McDonald, J. G., Russell, D. W., & Cyster, J. G. (2017) · Cell · doi:10.1016/j.cell.2017.09.029 · Cited by 348
Metadata
- Authors
- Blanc, M., Hsieh, W. Y., Robertson, K. A., Kropp, K. A., Forster, T., Shui, G., Lacaze, P., Watterson, S., Griffiths, S. J., Spann, N. J., Meljon, A., Talbot, S., Krishnan, K., Covey, D. F., Wenk, M. R., Craigon, M., Ruzsics, Z., Haas, J., Angulo, A., Griffiths, W. J., Glass, C. K., Wang, Y., & Ghazal, P.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 38
- Issue
- 1
- Pages
- 106-118
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2113504004
- Cited by
- 411
- References
- 4
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
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