Interleukin-4 and granulocyte-macrophage colony-stimulating factor mediates the upregulation of soluble vascular endothelial growth factor receptor-1 in RAW264.7 cells-a process in which p38 mitogen-activated protein kinase signaling has an important role.

Background/Purpose Soluble vascular endothelial growth factor receptor-1 (sVEGFR1) antagonizes angiogenesis by inhibiting the biological function of vascular endothelial growth factor (VEGF). Immature dendritic cells (imDCs) express high levels of sVEGFR1 during development and are antiangiogenic. This study aimed to investigate the changes in VEGFR1, sVEGFR1, and VEGF levels during the development of imDCs and explore the underlying signaling mechanisms. Methods To model the differentiation of imDCs from monocytes, RAW264.7 cells, a murine monocyte/macrophage cell line, were stimulated by interleukin-4 (IL-4; 10 ng/mL, 20 ng/mL, and 40 ng/mL) and/or by granulocyte-macrophage colony-stimulating factor (GM-CSF; 10 ng/mL, 20 ng/mL, and 50 ng/mL) and/or pretreated by the p38 inhibitor SB203580. The levels of VEGFR1, sVEGFR1, and VEGF were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot, and enzyme-linked immunosorbent assay (ELISA). Results IL-4 increased the VEGFR1 mRNA and sVEGFR1 levels in RAW264.7 ( p Conclusion IL-4 and GM-CSF increased sVEGFR1 levels, but did not significantly effect VEGF expression, and led to the antiangiogenesis properties of monocytes. p38 Mitogen-activated protein kinase signaling has an important role in the process.