title: 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.
abstract: OBJECTIVE
  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 < 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China; Department of Stomatology, Shuguang Branch of Shanghai Baoshan Hospital, Shanghai, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.affiliation: Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics in Shandong Province, Qilu Hospital, Shandong University, Jinan, PR China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Ketao
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics in Shandong Province, Qilu Hospital, Shandong University, Jinan, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China.
authors.forename: Fengcai
authors.initials: F
authors.lastname: Wei
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: angiogenesis; dendritic cell; granulocyte-macrophage colony-stimulating factor; interleukin-4; vascular endothelial growth factor receptor-1