HIV-1-infected and/or immune activated macrophages regulate astrocyte SDF-1 production through IL-1β
Article first published online: 30 AUG 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 54, Issue 6, pages 619–629, 1 November 2006
How to Cite
Peng, H., Erdmann, N., Whitney, N., Dou, H., Gorantla, S., Gendelman, H. E., Ghorpade, A. and Zheng, J. (2006), HIV-1-infected and/or immune activated macrophages regulate astrocyte SDF-1 production through IL-1β. Glia, 54: 619–629. doi: 10.1002/glia.20409
- Issue published online: 30 AUG 2006
- Article first published online: 30 AUG 2006
- Manuscript Accepted: 25 JUL 2006
- Manuscript Revised: 19 JUL 2006
- Manuscript Received: 30 OCT 2005
- National Institutes of Health. Grant Numbers: R01 NS 41858, P20 RR15635, P01 NS043985, P01NS31492
- HIV-1-associated dementia;
Stromal cell-derived factor 1 alpha (SDF-1α) and its receptor CXCR4 play important roles in the pathogenesis of human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) by serving as a HIV-1 co-receptor and affecting cell migration, virus-mediated neurotoxicity, and neurodegeneration. However, the underlying mechanisms regulating SDF-1 production during disease are not completely understood. In this report we investigated the role of HIV-1 infected and immune competent macrophage, the principal target cell and mediator of neuronal injury and death in HAD, in regulating SDF-1 production by astrocytes. Our data demonstrated that astrocytes are the primary cell type expressing SDF-1 in the brain. Immune-activated or HIV-1-infected human monocyte-derived-macrophage (MDM) conditioned media (MCM) induced a substantial increase in SDF-1 production by human astrocytes. This SDF-1 production was directly dependent on MDM IL-1β following both viral and immune activation. The MCM-induced production of SDF-1 was prevented by IL-1β receptor antagonist (IL-1Ra) and IL-1β siRNA treatment of human MDM. These laboratory observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HIVE). In these HIVE mice, reactive astrocytes showed a significant increase in SDF-1 expression, as observed by immunocytochemical staining. Similarly, SDF-1 mRNA levels were increased in the encephalitic region as measured by real time RT-PCR, and correlated with IL-1β mRNA expression. These observations provide direct evidence that IL-1β, produced from HIV-1-infected and/or immune competent macrophage, induces production of SDF-1 by astrocytes, and as such contribute to ongoing SDF-1 mediated CNS regulation during HAD. © 2006 Wiley-Liss, Inc.