Biochemical and Biophysical Research Communications
Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: The role for KDR and MMP-9☆
Section snippets
Materials and methods
Human cerebral endothelial cell culture. HCECs were purchased from Cell systems (St. Katharinen, Germany) and their homogeneous nature was confirmed by immunostaining with CD-31 antibody. Cultured cells were maintained at 37 °C in 5% CO2/95% ambient mixed air and the culture media were changed every two days. All experiments were performed on HCEC 2–4 passages. In IL-6 treatment experiments, HCECs were grown in the EC growth medium (Clonetics, Walkersville, MD) in 35 mm polystyrene plates to 90%
Effect of IL-6 on VEGF expression in HCECs
Involvement of IL-6 in angiogenesis is related to VEGF production [16]. Because mitogenic activity of HCECs could be stimulated by VEGF or IL-6, we therefore investigated the interaction between IL-6 and VEGF expression. The data showed that IL-6 stimulates VEGF expression by two-fold in both mRNA and protein levels as compared to the control group (Figs. 1A and B). Dose–response results indicated that this effect was maximal at 100 ng/ml IL-6. The maximal increase in the mRNA expression was at
Discussion
Our results provide evidence that IL-6 augments VEGF-induced HCEC proliferation and migration, up-regulates KDR phosphorylation, and enhances MMP-9 activity. Our findings reveal a physiologically important feedback mechanism for the amplification of the angiogenic response in vitro, which may be relevant in many pathological situations.
IL-6 can be produced by HCECs and IL-6 receptors are expressed throughout CNS, including endothelial cells, astrocytes, microglia, and neurons [3], [4]. The
Acknowledgments
The authors thank Voltaire Gungab for editorial assistance and the collaborative support of the staff of the Center for Cerebrovascular Research <http://avm.ucsf.edu/>.
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The study was supported by a Grant from the National Institutes of Health P01 NS44144 (GYY, WLY), R01 NS27713 (WLY), and R21 NS45123 (GYY).