摘要BACKGROUND: Studies of several animal models of central nervous system diseases have shown that neural progenitor cells (NPCs) can migrate to injured tissues. Stromal cell-derived factor 1 alpha (SDF-1α), and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE: To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in SDF-1α/CXCR4 axis-induced migration of NPCs.DESIGN, TIME AND SETTING: An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007.MATERIALS: SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R&D Systems, USA. TNF-α was purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS: NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES: The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry.RESULTS: Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs (P < 0.01), and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect (P < 0.05). Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α (P < 0.01). CONCLUSION: These results demonstrated that SDF-1α significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1α gradient by upregulating CXCR4 expression in NPCs.