title: Interleukin-8 induces the endothelial cell migration through the Rac 1/RhoA-p38MAPK pathway.
abstract: OBJECTIVE
  Endothelial cell migration is essential for tumor angiogenesis, and interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to investigate the molecular mechanism of IL-8 induced endothelial cell migration in vitro.
  
  
  METHODS
  Fluorescence microscope was used to study the distribution of cytoskeleton. The expression of Rac1 and RhoA protein was detected by western blotting. After endothelial cells were transfected by lipofectamine 2000 reagent, the Transwell chamber motility assay was applied to observe the migration of endothelial cells induced by IL-8. The active p38MAPK (mitogen-activated protein kinase) was evaluated by the p38MAPK activation assay.
  
  
  RESULTS
  We demonstrated that IL-8 activated cell migration can be impaired by p38MAPK inhibitor, suggesting the participation of p38MAPK in the cell migration. Our results indicated that p38MAPK signaling is required for membrane ruffles, lamellipodia extensions, and actin stress fibers formation induced by IL-8. Furthermore, p38MAPK inhibitor led to increased Rac1 and RhoA expression in IL-8 treated EA.hy926 cells. In addition, IL-8 induced p38MAPK activation was suppressed by dominant-negative mutant for Rac1 and RhoA.
  
  
  CONCLUSIONS
  Our study demonstrates that IL-8-Rac1/RhoA-p38MAPK signaling pathway plays a vital role in the IL-8-induced endothelial cell migration, and it provides new insight into the molecular mechanisms by which IL-8 contributes to tumor angiogenesis and metastasis.
authors: Institute of Biomedical Engineering, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors: Y
authors: Y
authors: Lai
authors: X H
authors: XH
authors: Liu
authors: Y
authors: Y
authors: Zeng
authors: Y
authors: Y
authors: Zhang
authors: Y
authors: Y
authors: Shen
authors: Ye
authors: Y
authors: Liu
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000201:enzymology / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; C107953:RAC1 protein, human; C066737:RHOA protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein