title: Roles of activated astrocyte in neural stem cell proliferation and differentiation.
abstract: Recent studies demonstrated that the molecules secreted from astrocytes play important roles in the cell fate determination of neural stem cells (NSCs). However, the exact molecules involved and its possible mechanisms in the process remain largely unknown. In this study, astrocyte-conditioned medium (ACM) obtained from astrocytes unstimulated or stimulated by lipopolysaccharide was prepared to treat NSCs. The results showed that both the proliferation and differentiation of NSCs treated with stimulated ACMs were significantly increased compared with those treated with unstimulated ACM. Interleukin-6 (IL-6) antibody neutralization of the ACMs decreased NSC proliferation and astrogliogenesis, while NSC neurogenesis was increased. In contrast, recombinant IL-6 cytokine increased NSC proliferation and astrogliogenesis, but decreased neurogenesis. Furthermore, the expression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) protein as well as serial of basic helix-loop-helix transcription factors (bHLH) mRNA in NSCs exposed to stimulated ACMs significantly increased, respectively. The expression levels of p-stat3 protein and bHLH mRNA of NSCs were significantly altered after adding anti-IL-6 antibody or recombinant IL-6, respectively. The data suggest that IL-6 secreted from activated astrocytes participates in ACM-induced proliferation and differentiation of NSCs via the phosphorylation of stat3 signals and the expression of bHLH transcription factors.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, No.44, Wenhua Xi Road, Jinan, Shandong, 250012, PR China.
authors.forename: Fu-wu
authors.initials: FW
authors.lastname: Wang
authors.forename: Hong-bo
authors.initials: HB
authors.lastname: Hao
authors.forename: Shi-dou
authors.initials: SD
authors.lastname: Zhao
authors.forename: Yan-min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Liu
authors.forename: Shang-ming
authors.initials: SM
authors.lastname: Liu
authors.forename: Qiu-huan
authors.initials: QH
authors.lastname: Yuan
authors.forename: Lu-jun
authors.initials: LJ
authors.lastname: Bing
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Ai-jun
authors.initials: AJ
authors.lastname: Hao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha