HIV-1-infected and/or immune-activated macrophage-secreted TNF-α affects human fetal cortical neural progenitor cell proliferation and differentiation

Hui Peng, Nicholas Whitney, Yumei Wu, Changhai Tian, Huanyu Dou, You Zhou, Jialin C Zheng

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Neurogenesis, tied to the proliferation, migration and differentiation of neural progenitor cells (NPC) is affected during neurodegenerative diseases, but how neurogenesis is affected during HIV-1 associated dementia (HAD) has not been fully addressed. Here we test the hypothesis that HIV-1-infected and/or immune-activated brain macrophages affect NPC proliferation and differentiation through the regulation of cytokines. We showed that human monocyte-derived macrophages (MDM) conditioned medium (MCM) induces a dose dependant increase in NPC proliferation. Conditioned media from lipopolysaccharide (LPS)-activated MDM (LPS-MCM) or HIV-infected MCM (HIV-MCM) induced a profound increase in NPC proliferation. HIV-infected and LPS-activated MCM (HIV+LPS_MCM) induced the most robust increase in NPC proliferation. Moreover, LPS-MCM and HIV+LPS-MCM decreased β-III-tubulin and increased GFAP expression, demonstrating an induction of gliogenesis and inhibition of neurogenesis. The increase of NPC proliferation and gliogenesis correlated with increases in production of TNF-α- by infected/ activated MDM. Although both IL-1β and TNF-α induced NPC proliferation and gliogenesis, these effects were only partially abrogated by soluble TNF-α receptors R1 and R2 (TNF-RlR2), but not by the IL-1 receptor antagonist (IL-1ra). This indicated that the HIV-1-infected/ LPS-activated MCM-mediated effects were, in part, through TNF-α. These observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HIVE). In these HIVE mice, NPC injected with HIV-infected MDM showed more astrocyte differentiation and less neuronal differentiation compared to NPC injection alone. These observations demonstrated that HIV-1-infected and immune-activated MDM could affect neurogenesis through induction of NPC proliferation, inhibition of neurogenesis, and activation of gliogenesis.

Original languageEnglish (US)
Pages (from-to)903-916
Number of pages14
JournalGlia
Volume56
Issue number8
DOIs
StatePublished - Jun 1 2008

Fingerprint

Conditioned Culture Medium
HIV-1
Cell Differentiation
Stem Cells
Macrophages
Cell Proliferation
Lipopolysaccharides
Neurogenesis
HIV
Encephalitis
Interleukin-1 Receptors
SCID Mice
Tumor Necrosis Factor Receptors
Tubulin
Interleukin-1
Astrocytes
Neurodegenerative Diseases
Dementia
Cytokines
Injections

Keywords

  • Differentiation
  • HIV-1
  • Macrophage
  • Neural progenitor cell
  • Proliferation
  • TNF-α

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

HIV-1-infected and/or immune-activated macrophage-secreted TNF-α affects human fetal cortical neural progenitor cell proliferation and differentiation. / Peng, Hui; Whitney, Nicholas; Wu, Yumei; Tian, Changhai; Dou, Huanyu; Zhou, You; Zheng, Jialin C.

In: Glia, Vol. 56, No. 8, 01.06.2008, p. 903-916.

Research output: Contribution to journalArticle

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abstract = "Neurogenesis, tied to the proliferation, migration and differentiation of neural progenitor cells (NPC) is affected during neurodegenerative diseases, but how neurogenesis is affected during HIV-1 associated dementia (HAD) has not been fully addressed. Here we test the hypothesis that HIV-1-infected and/or immune-activated brain macrophages affect NPC proliferation and differentiation through the regulation of cytokines. We showed that human monocyte-derived macrophages (MDM) conditioned medium (MCM) induces a dose dependant increase in NPC proliferation. Conditioned media from lipopolysaccharide (LPS)-activated MDM (LPS-MCM) or HIV-infected MCM (HIV-MCM) induced a profound increase in NPC proliferation. HIV-infected and LPS-activated MCM (HIV+LPS_MCM) induced the most robust increase in NPC proliferation. Moreover, LPS-MCM and HIV+LPS-MCM decreased β-III-tubulin and increased GFAP expression, demonstrating an induction of gliogenesis and inhibition of neurogenesis. The increase of NPC proliferation and gliogenesis correlated with increases in production of TNF-α- by infected/ activated MDM. Although both IL-1β and TNF-α induced NPC proliferation and gliogenesis, these effects were only partially abrogated by soluble TNF-α receptors R1 and R2 (TNF-RlR2), but not by the IL-1 receptor antagonist (IL-1ra). This indicated that the HIV-1-infected/ LPS-activated MCM-mediated effects were, in part, through TNF-α. These observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HIVE). In these HIVE mice, NPC injected with HIV-infected MDM showed more astrocyte differentiation and less neuronal differentiation compared to NPC injection alone. These observations demonstrated that HIV-1-infected and immune-activated MDM could affect neurogenesis through induction of NPC proliferation, inhibition of neurogenesis, and activation of gliogenesis.",
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AU - Dou, Huanyu

AU - Zhou, You

AU - Zheng, Jialin C

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