Directed migration of human neural progenitor cells to interleukin-1β is promoted by chemokines stromal cell-derived factor-1 and monocyte chemotactic factor-1 in mouse brains

BACKGROUND: Neurogenesis, 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. METHODS: The 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. RESULTS: SDF-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. CONCLUSIONS: In 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.