The Crosstalk Effects Of Chemokine And IL-6 Family Cytokine On Regulation Of Migration And Differentiation Of Neural Stem Cells

Neural stem cells (NSCs) are certain kind of cells that locate in the central nervous system and have the ability of differentiating into neurons and glial cells. The research on NSCs are provided with significant values for it would deepen the understanding of nervous system's origination and development as well as give instructions to therapy and recovery of nervous system diseases.We first cultured NSCs, isolated from rat forebrain, in serum-free medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). The NSCs are floated as multi-cell aggregates called neurospheres. When dissociated into a single-cell suspension and replated in the medium, the neurospheres form again after several days. Moreover, the neurospheres are Nestin positive and could differentiate to neurons and glial cells when seeded on ploy-L-lysine coated substrate.We found that the cytokine Hyper-IL-6 (H-IL-6) could significantly suppress the cell mobility of NSCs ex vivo in a dose-dependent manner. Also we detected that the mRNA levels of chemokine SDF1, chemokine receptor CXCR4 and CX3CR1 are rapidly increased in adherent cells. However, after inducement of H-IL-6, the expression of CXCR4 and PLP, marker of oligodendrocytes, are decreased obviously, whereas SOCS family proteins which are main inhibitors in JAK/STAT pathway show apparently rises in mRNA expressions.Our results indicate that H-IL-6 can regulate migration and differentiation of NSCs, and there are two possible mechanisms of such phenomenon: 1. H-IL-6 reduces expression of CXCR4; 2. H-IL-6 activates JAK/STAT pathway, brings increases in mRNA levels of SOCS family protein. By binding to CXCR4, SOCS3 restrains its activation. Our results also show that H-IL-6 could inhibit NSCs differentiating to oligodendrocytes. The chemokines and cytokines such as IL-6 may have crosstalk effects on regulating migration and differentiation of NSCs. Some deeper researches of this field will depict a vivid and detailed network structure of signal transduction and regulation, opening new ways for neurobiology research.