Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.immuni.2012.11.004
Title: The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response
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.
Issue Date: 24-Jan-2013
Citation: 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. (2013-01-24). The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response. Immunity 38 (1) : 106-118. ScholarBank@NUS Repository. https://doi.org/10.1016/j.immuni.2012.11.004
Abstract: 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. © 2013 Elsevier Inc.
Source Title: Immunity
URI: http://scholarbank.nus.edu.sg/handle/10635/115331
ISSN: 10747613
DOI: 10.1016/j.immuni.2012.11.004
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

231
checked on Jan 26, 2022

WEB OF SCIENCETM
Citations

226
checked on Jan 26, 2022

Page view(s)

89
checked on Jan 27, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.