CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation, migration and capillary-like structure formation

Microvasc Res. 2011 Nov;82(3):318-25. doi: 10.1016/j.mvr.2011.06.011. Epub 2011 Jul 1.


CXCR1 and CXCR2 are receptors for angiogenic ELR+CXC chemokines and are differentially expressed on endothelial cells; however, their functional significance in angiogenesis remains unclear. In this study, we determined the functional significance of these receptors in modulating endothelial cell phenotype by knocking-down the expression of CXCR1 and/or CXCR2 in human microvascular endothelial cells (HMEC-1) using short-hairpin RNA (shRNA). Cell proliferation, migration, invasion and capillary-like structure (CLS) formation were analyzed. Our data demonstrate that knock-down of CXCR1 and/or CXCR2 expression inhibited endothelial cell proliferation, survival, migration, invasion and CLS formation. Additionally, we examined the mechanism of CXCL8-dependent CXCR1 and/or CXCR2 mediated phenotypic changes by evaluating ERK phosphorylation and cytoskeletal rearrangement and observed inhibition of ERK phosphorylation and cytoskeletal rearrangement in HMEC-1-shCXCR1, HMEC-1-shCXCR2 and HMEC-1-shCXCR1/2 cells. Together, these data demonstrate that CXCR1 and CXCR2 expression plays a critical role in regulating multiple biological activities in human microvascular endothelial cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line
  • Cell Movement*
  • Cell Proliferation*
  • Cell Survival
  • Endothelial Cells / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Genotype
  • Humans
  • Interleukin-8 / metabolism*
  • Neovascularization, Physiologic*
  • Phenotype
  • Phosphorylation
  • RNA Interference*
  • Receptors, Interleukin-8A / genetics
  • Receptors, Interleukin-8A / metabolism*
  • Receptors, Interleukin-8B / genetics
  • Receptors, Interleukin-8B / metabolism*
  • Stress Fibers / metabolism
  • Transfection


  • CXCL8 protein, human
  • Interleukin-8
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Extracellular Signal-Regulated MAP Kinases