title: Interleukin-6 trans-signalling induces vascular endothelial growth factor synthesis partly via Janus kinases-STAT3 pathway in human mesothelial cells.
abstract: OBJECTIVE
  Interleukin-6 (IL-6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL-6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells.
  
  
  METHODS
  Human mesothelial cells (Met-5A) were incubated with different concentrations of glucose and mannitol, and the effect of glucose and mannitol on the expression of IL-6 was determined. Then, the cells were stimulated by IL-6 with or without two soluble receptors of IL-6 (sIL-6R or sgp130), and VEGF synthesis was detected. Finally, the cells were incubated with IL-6/sIL-6R combined with or without the inhibitor of Janus kinases (JAK) AG490. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and its intracellular translocation were examined.
  
  
  RESULTS
  1. High glucose and mannitol could upregulate IL-6 mRNA expression and IL-6 secretion in mesothelial cells significantly, and there was no difference of its effect between high glucose and mannitol. 2. Met-5A was a cell line with a single IL-6 receptor. The IL-6/sIL-6R complex induced VEGF synthesis of mesothelial cells, which was alleviated by sgp130 or AG490. IL-6 trans-signalling could induce the phosphorylation of STAT3, which is recruited to the cellular nucleus of Met-5A cells.
  
  
  CONCLUSIONS
  The present study might provide evidence that high glucose upregulates IL-6 synthesis in Met-5A cells, to some extent, depending on its osmolality and that IL-6 trans-signalling could induce VEGF synthesis partly dependent on the JAK/STAT3 pathway.
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Xiaoxiao
authors: X
authors: Yang
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Aiwu
authors: A
authors: Lin
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Na
authors: N
authors: Jiang
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Hao
authors: H
authors: Yan
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Zhaohui
authors: Z
authors: Ni
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Jiaqi
authors: J
authors: Qian
authors: Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
authors: Wei
authors: W
authors: Fang
mesh_terms: D021581:Active Transport, Cell Nucleus; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D005947:Glucose / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008353:Mannitol / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: C508600:IL6 protein, human; C508603:IL6R protein, human; C494199:IL6ST protein, human; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D050822:Cytokine Receptor gp130; D008353:Mannitol; D053612:Janus Kinases; D005947:Glucose
keywords: IL-6 trans-signalling; JAK/STAT3; peritoneal dialysis; vascular endothelial growth factor