发明名称 |
TREATMENT OF HIV-1 BY MODULATION OF VPR ACTIVATION OF THE M-CSF PROMOTER |
摘要 |
Macrophage colony-stimulating factor (M-CSF) is important for human immunodeficiency virus-type 1 (HIV-1) infection, replication and survival of infected cells. The mechanism(s) by which HIV-1 infection increases M-CSF production are, however, poorly understood. Here, we report that HIV-1 Vpr enhances M-CSF promoter activity and production in primary human monocytes and macrophages. Vpr activates M-CSF transcription through four C/EBP beta binding sites present within the M-CSF promoter, possibly through increased phosphorylation of C/EBP beta. RU486 (mifepristone) blocked Vpr-mediated up-regulation of M-CSF, suggesting that Vpr activates M-CSF promoter activity via the glucocorticoid pathway. The invention provides new avenues for therapeutic interventions in HIV-1 infection and other diseases involving M-CSF dysregulation (including malignancy, osteoporosis, autoimmune disorders, arthritis, and obesity) using glucocorticoid antagonists and modulators of C/EBP beta activity.
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申请公布号 |
WO2007140253(A3) |
申请公布日期 |
2008.08.28 |
申请号 |
WO2007US69659 |
申请日期 |
2007.05.24 |
申请人 |
TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OFHIGHER EDUCATION;RAPPAPORT, JAY;HAINE, VALERIE;FISCHER-SMITH, TRACY |
发明人 |
RAPPAPORT, JAY;HAINE, VALERIE;FISCHER-SMITH, TRACY |
分类号 |
A61K31/7088;C07H21/04;C12N15/33;C12N15/48;C12N15/49 |
主分类号 |
A61K31/7088 |
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