HIV-1-infected and/or immune activated macrophages regulate astrocyte SDF-1 production through IL-1β

Hui Peng, Nathan Erdmann, Nicholas Whitney, Huangyu Dou, Santhi Gorantla, Howard E. Gendelman, Anuja Ghorpade, Jialin Zheng

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78 Scopus citations

Abstract

Stromal cell-derived factor 1 alpha (SDF-1α) and its receptor CXCR4 play important roles in the pathogenesis of human immunodeficiency virus type one (H1V-1)-associated dementia (HAD) by serving as a HTV-1 co-receptor and affecting cell migration, virus-mediated neurotoxicity, and neurode-generation. 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 HTV-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-IRa) and IL-1β siRNA treatment of human MDM. These laboratory observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HTVE). 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-I by astrocytes, and as such contribute to ongoing SDF-1 mediated CNS regulation during HAD.

Original languageEnglish
Pages (from-to)619-629
Number of pages11
JournalGLIA
Volume54
Issue number6
DOIs
StatePublished - Nov 2006

Keywords

  • Astrocytes
  • HIV-1-associated dementia
  • IL-1β
  • Macrophages
  • SDF-1

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    Peng, H., Erdmann, N., Whitney, N., Dou, H., Gorantla, S., Gendelman, H. E., Ghorpade, A., & Zheng, J. (2006). HIV-1-infected and/or immune activated macrophages regulate astrocyte SDF-1 production through IL-1β. GLIA, 54(6), 619-629. https://doi.org/10.1002/glia.20409