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.
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