Eotaxin increases monolayer permeability of human coronary artery endothelial cells

Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2146-52. doi: 10.1161/ATVBAHA.109.194134. Epub 2009 Sep 24.


Objective: The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs).

Methods and results: Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin, and claudin-1 in a concentration-dependent manner as determined by real-time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580, and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased the phosphorylation of Stat3 and nuclear translocation of NF-kappaB in HCAECs.

Conclusions: Eotaxin increases vascular permeability through CCR3, the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-kB pathways in HCAECs.

Publication types

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

MeSH terms

  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology
  • Cells, Cultured
  • Chemokine CCL11 / pharmacology*
  • Chemokine CCL11 / physiology
  • Claudin-1
  • Coronary Vessels / cytology
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / physiology
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • NF-kappa B / metabolism
  • Occludin
  • Oxidative Stress / drug effects
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR3 / metabolism
  • STAT3 Transcription Factor / metabolism
  • Zonula Occludens-1 Protein
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • CCL11 protein, human
  • CCR3 protein, human
  • CLDN1 protein, human
  • Chemokine CCL11
  • Claudin-1
  • Membrane Proteins
  • NF-kappa B
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, CCR3
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • p38 Mitogen-Activated Protein Kinases