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Volume 49, Number 3, June 2016

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 

Lin Xia, Zhaogang Dong, Yun Zhang, Xiaoying Zhang, Xiaobin Song, Mingxia Sun, Yingwei Hu, Shaohua Liu, Ketao Wang, Xun Qu, Fengcai Wei

Received: October 3, 2016    Revised: October 3, 2016    Accepted: October 3, 2016   


Corresponding author:

Corresponding author. Fengcai Wei, Department of Oral Maxillofacial Surgery at Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, PR China. 


Background and 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. 



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). 



IL-4 increased the VEGFR1 mRNA and sVEGFR1 levels in RAW264.7 (p < 0.05). This increase was inhibited by SB203580. Granulocyte-macrophage colony-stimulating factor increased the sVEGFR1 levels, but it had no significant effect on VEGFR1 mRNA levels. SB203580 decreased the expression of VEGFR1 mRNA induced by GM-CSF, whereas sVEGFR1 was unaffected. IL-4 had a greater effect on sVEGFR1 levels, compared to GM-CSF. 



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. 


Key words:

angiogenesis, dendritic cell, granulocyte-macrophage colony-stimulating factor, interleukin-4, vascular endothelial growth factor receptor-1