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(HI...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.展开更多
基金This work was supported in part by research grants by the National Institutes of Health:R01 NS 41858–01,R01 NS 061642–01,R01NS61642-2 S1,R21 MH 083525–01,P01 NS043985,and P20 RR15635-01 to JZNational Natural Science Foundation of China(NSFC)#81028007 to JZ,#81101457 to YWScientific Research Foundation for the Returned Overseas Chinese Scholars No.HG3402 to YW.We kindly acknowledge Dr.Changhai Tian,Li Wu,and Dr.Jim Eudy(UNMC microarray core facility).Kristin Leland Wavrin provided valuable comments and suggestions about the manuscript.Dr.Charles Kuszynski and Linda Wilkie performed the FACS analysis.Julie Ditter,Robin Taylor,Myhanh Che,Na Ly,and Emilie Scoggins provided outstanding administrativesupport.
文摘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.
