Abstract
BackgroundNeurogenesis, including the proliferation, migration and differentiation of neural progenitor cells (NPCs), is impaired in HIV-1 associated dementia (HAD). We previously demonstrated HIV-1-infected macrophages (HIV-MDM) regulate stromal cell-derived factor 1 (SDF-1) production in astrocytes through Interleukin-1β (IL-1β). Chemokines are known to induce NPC migration; however, it remains unclear how chemokines produced in inflammation regulate NPC migration.MethodsThe secretion of SDF-1 and Monocyte chemotactic preotein-1 (MCP-1) in astrocytes upon IL-1β stimulation was measured by ELISA assay. Human NPCs were injected parallel along with IL-1β, SDF-1 or MCP-1 intracranially into basal ganglion 1 mm apart in SCID mice, and immunofluorescent staining was used to study the survival and migration of injected human NPCs.ResultsSDF-1 and MCP-1 are secreted by astrocytes upon IL-1β stimulation in a time-dependent manner. Injected human NPCs survived in SCID mice and migrated towards sites of IL-1β, SDF-1 and MCP-1 injection.ConclusionsIn conclusion, chemokines SDF-1 or MCP-1 secreted by astrocytes in the presence of IL-1β injection are attractive to NPCs injected into SCID mouse brains, suggesting that SDF-1 and MCP-1 play important roles in NPC migration during neuroinflammation.
Highlights
Neurogenesis, including the proliferation, migration and differentiation of neural progenitor cells (NPCs), is impaired in HIV-1 associated dementia (HAD)
stromal cell-derived factor 1 (SDF-1), and Monocyte chemotactic preotein-1 (MCP-1), were secreted by astrocytes time- and dose-dependently upon IL-1β stimulation, and human NPCs migrated to SDF-1 and MCP-1 in the SCID mouse model
With the expression of both chemokine receptors CXCR4 and CCR2 in human NPC [13,24], the in vitro data suggested that chemokines SDF-1 and MCP-1 promote NPC migration in vitro
Summary
Neurogenesis, including the proliferation, migration and differentiation of neural progenitor cells (NPCs), is impaired in HIV-1 associated dementia (HAD). Neurogenesis, which includes proliferation, migration and differentiation of neural progenitor cells (NPCs), in adults has been observed to be impaired in HAD patients [1]. MCP-1 plays a critical role in neuroblast migration after focal cerebral ischemia and induces migration and differentiation of subventricular zone cells after stroke [19], suggesting MCP-1 as a potential mediator for NPC migration under HIV-1 inflammation. Hypoxia-induced astrocytes promote the migration of NPCs via vascular endothelial growth factor, stem cell factor, SDF-1 and MCP-1 upregulation in vitro [14], further indicating that both SDF-1 and MCP-1 may play critical roles in NPC migration
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