Chemokines released from astrocytes promote chemokine receptor 5-mediated neuronal cell differentiation

Astrocytes are one of major glial cell types in the central nervous system (CNS), and can support many functions of neuronal cells. In the present study, we demonstrated that the differentiation of rat embryonic neuronal cells was promoted by treatment with astrocyte and microglia-conditioned medium. Cytokine assays identified that the IL-4, MIP-1, KC, and RANTES as were released from astrocyte, and these chemokines promote differentiation of rat embryonic neuronal cells. However, chemokine-promoted neuronal cell differentiation was suppressed by antibodies of these chemokines and their receptor (CCR5). CCR5 and neuronal cell differentiation marker proteins were found to be colocalized, and their expressions were enhanced by chemokines. Furthermore, the differentiation of neuronal cells from CCR5 knock-out mice and of neuronal cells from mice knocked down with the CCR5 siRNA were significantly reduced and delayed. Bradykinin elevated calcium influx in the embryonic neuronal cells. These data suggest that specific chemokines derived from astrocytes may significantly have influence on the CCR5-mediated differentiation of embryonic neuronal cells.