TY - JOUR
T1 - HIV-1-infected and/or immune-activated macrophage-secreted TNF-α affects human fetal cortical neural progenitor cell proliferation and differentiation
AU - Peng, Hui
AU - Whitney, Nicholas
AU - Wu, Yumei
AU - Tian, Changhai
AU - Dou, Huanyu
AU - Zhou, You
AU - Zheng, Jialin
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Differentiation
KW - HIV-1
KW - Macrophage
KW - Neural progenitor cell
KW - Proliferation
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=46749113119&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46749113119&partnerID=8YFLogxK
U2 - 10.1002/glia.20665
DO - 10.1002/glia.20665
M3 - Article
C2 - 18383342
AN - SCOPUS:46749113119
SN - 0894-1491
VL - 56
SP - 903
EP - 916
JO - GLIA
JF - GLIA
IS - 8
ER -