Abstract

We found that a monokine induced by interferon-gamma (Mig, CXCL9), which belongs to the CXC chemokine subfamily, acts as a neurotrophic factor on PC12 cells and rat primary sympathetic neurons. PC12 cells were shown to express a single class of high affinity binding sites for Mig (670 receptors/cell, Kd = 2.9 nm). Mig induced neurite outgrowth in PC12 cells in a dose-dependent manner. Comparison of extracellular signal-regulated kinase signaling pathways between Mig and nerve growth factor (NGF) revealed that these pathways are crucial for Mig action as well as NGF. K252a, an inhibitor of tyrosine autophosphorylation of tyrosine kinase receptors (Trks) did not inhibit the action of Mig, suggesting that Mig action occurs via a different receptor from that of NGF. Furthermore, Mig as well as NGF promoted PC12 survival under serum-free conditions and activated Akt/protein kinase B downstream from phosphatidylinositol 3-kinase (PI3K). Because the PI3K inhibitor LY294002 prevented the Mig- and NGF-induced survival effect, this effect is probably mediated by the PI3K signaling pathway. Mig also promoted survival of rat primary sympathetic neurons that die when deprived of NGF. These results suggest that chemokines, including Mig (CXCL9) have neurotrophic effects on the nervous system.

Highlights

  • Nerve growth factor (NGF),2 a prominent neurotrophic factor, plays a crucial role in promoting growth, differentiation, and survival of sympathetic nerve cells [20]

  • We found that one of the CXC chemokines, monokine induced by interferon-␥ (Mig, CXCL9) promotes the neuronal differentiation and survival of PC12 cells

  • Our results indicated that one of the CXC chemokines, monokine induced by interferon-␥ (Mig, CXCL9) stimulates neurite extension in PC12 cells

Read more

Summary

Introduction

Nerve growth factor (NGF),2 a prominent neurotrophic factor, plays a crucial role in promoting growth, differentiation, and survival of sympathetic nerve cells [20]. We found that one of the CXC chemokines, monokine induced by interferon-␥ (Mig, CXCL9) promotes the neuronal differentiation and survival of PC12 cells. Like human Mig, rat Mig strongly stimulated neurite outgrowth in PC12 cells in a dose-dependent manner (supplemental Fig. S1).

Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call