Journal article 1040 views
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response
Immunity, Volume: 38, Issue: 1, Pages: 106 - 118
Swansea University Authors:
Yuqin Wang , William Griffiths
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DOI (Published version): 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 product...
Published in: | Immunity |
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ISSN: | 1074-7613 |
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2013
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URI: | https://cronfa.swan.ac.uk/Record/cronfa13836 |
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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.</abstract><type>Journal Article</type><journal>Immunity</journal><volume>38</volume><journalNumber>1</journalNumber><paginationStart>106</paginationStart><paginationEnd>118</paginationEnd><publisher/><issnPrint>1074-7613</issnPrint><issnElectronic/><keywords/><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2013</publishedYear><publishedDate>2013-12-31</publishedDate><doi>10.1016/j.immuni.2012.11.004</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2013-11-08T10:45:02.6337528</lastEdited><Created>2013-01-04T15:33:14.5809495</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Mathieu</firstname><surname>Blanc</surname><order>1</order></author><author><firstname>Wei&nbsp;Yuan</firstname><surname>Hsieh</surname><order>2</order></author><author><firstname>Kevin&nbsp;A</firstname><surname>Robertson</surname><order>3</order></author><author><firstname>Kai&nbsp;A</firstname><surname>Kropp</surname><order>4</order></author><author><firstname>Thorsten</firstname><surname>Forster</surname><order>5</order></author><author><firstname>Guanghou</firstname><surname>Shui</surname><order>6</order></author><author><firstname>Paul</firstname><surname>Lacaze</surname><order>7</order></author><author><firstname>Steven</firstname><surname>Watterson</surname><order>8</order></author><author><firstname>Samantha&nbsp;J</firstname><surname>Griffiths</surname><order>9</order></author><author><firstname>Nathanael&nbsp;J</firstname><surname>Spann</surname><order>10</order></author><author><firstname>Anna</firstname><surname>Meljon</surname><order>11</order></author><author><firstname>Simon</firstname><surname>Talbot</surname><order>12</order></author><author><firstname>Kathiresan</firstname><surname>Krishnan</surname><order>13</order></author><author><firstname>Douglas&nbsp;F</firstname><surname>Covey</surname><order>14</order></author><author><firstname>Markus&nbsp;R</firstname><surname>Wenk</surname><order>15</order></author><author><firstname>Marie</firstname><surname>Craigon</surname><order>16</order></author><author><firstname>Zsolts</firstname><surname>Ruzsics</surname><order>17</order></author><author><firstname>Jürgen</firstname><surname>Haas</surname><order>18</order></author><author><firstname>Ana</firstname><surname>Angulo</surname><order>19</order></author><author><firstname>William&nbsp;J</firstname><surname>Griffiths</surname><order>20</order></author><author><firstname>Christopher&nbsp;K</firstname><surname>Glass</surname><order>21</order></author><author><firstname>Yuqin</firstname><surname>Wang</surname><orcid>0000-0002-3063-3066</orcid><order>22</order></author><author><firstname>Peter</firstname><surname>Ghazal</surname><order>23</order></author><author><firstname>William</firstname><surname>Griffiths</surname><orcid>0000-0002-4129-6616</orcid><order>24</order></author></authors><documents/><OutputDurs/></rfc1807> |
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2013-11-08T10:45:02.6337528 v2 13836 2013-01-04 The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2013-01-04 BMS 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. Journal Article Immunity 38 1 106 118 1074-7613 31 12 2013 2013-12-31 10.1016/j.immuni.2012.11.004 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-11-08T10:45:02.6337528 2013-01-04T15:33:14.5809495 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Mathieu Blanc 1 Wei Yuan Hsieh 2 Kevin A Robertson 3 Kai A Kropp 4 Thorsten Forster 5 Guanghou Shui 6 Paul Lacaze 7 Steven Watterson 8 Samantha J Griffiths 9 Nathanael J Spann 10 Anna Meljon 11 Simon Talbot 12 Kathiresan Krishnan 13 Douglas F Covey 14 Markus R Wenk 15 Marie Craigon 16 Zsolts Ruzsics 17 Jürgen Haas 18 Ana Angulo 19 William J Griffiths 20 Christopher K Glass 21 Yuqin Wang 0000-0002-3063-3066 22 Peter Ghazal 23 William Griffiths 0000-0002-4129-6616 24 |
title |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response |
spellingShingle |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response Yuqin Wang William Griffiths |
title_short |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response |
title_full |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response |
title_fullStr |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response |
title_full_unstemmed |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response |
title_sort |
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response |
author_id_str_mv |
c92729b58622f9fdf6a0e7d8f4ce5081 3316b1d1b524be1831790933eed1c26e |
author_id_fullname_str_mv |
c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang 3316b1d1b524be1831790933eed1c26e_***_William Griffiths |
author |
Yuqin Wang William Griffiths |
author2 |
Mathieu Blanc Wei Yuan Hsieh Kevin A Robertson Kai A Kropp Thorsten Forster Guanghou Shui Paul Lacaze Steven Watterson Samantha J Griffiths Nathanael J Spann Anna Meljon Simon Talbot Kathiresan Krishnan Douglas F Covey Markus R Wenk Marie Craigon Zsolts Ruzsics Jürgen Haas Ana Angulo William J Griffiths Christopher K Glass Yuqin Wang Peter Ghazal William Griffiths |
format |
Journal article |
container_title |
Immunity |
container_volume |
38 |
container_issue |
1 |
container_start_page |
106 |
publishDate |
2013 |
institution |
Swansea University |
issn |
1074-7613 |
doi_str_mv |
10.1016/j.immuni.2012.11.004 |
college_str |
Faculty of Medicine, Health and Life Sciences |
hierarchytype |
|
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facultyofmedicinehealthandlifesciences |
hierarchy_top_title |
Faculty of Medicine, Health and Life Sciences |
hierarchy_parent_id |
facultyofmedicinehealthandlifesciences |
hierarchy_parent_title |
Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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description |
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. |
published_date |
2013-12-31T03:15:49Z |
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1763750287665790976 |
score |
11.013371 |