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

摘要

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-1βstimulation 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-1βstimulation 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-1βinjection are attractive to NPCs injected into SCID mouse brains,suggesting that SDF-1 and MCP-1 play important roles in NPC migration during neuroinflammation.