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
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Cited by
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Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
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Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
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ATF3 Is a Key Regulator of Macrophage IFN Responses
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Infectious agents and Alzheimer's disease
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Cholesterol metabolism: from lipidomics to immunology
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Self-citationPascual-García, M., Rué, L., León, T., Julve, J., Carbó, J. M., Matalonga, J., Auer, H., Celada, A., Escolà-Gil, J. C., Steffensen, K. R., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201393 · Cited by 51
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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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