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.
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 MAPKp38. 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 MAPKp38, Stat3, and NF-kB pathways in HCAECs.
Authors: Ravindra B Kodali; William J H Kim; Irfan I Galaria; Christine Miller; Alison D Schecter; Sergio A Lira; Mark B Taubman Journal: Arterioscler Thromb Vasc Biol Date: 2004-05-06 Impact factor: 8.311
Authors: P D Ponath; S Qin; D J Ringler; I Clark-Lewis; J Wang; N Kassam; H Smith; X Shi; J A Gonzalo; W Newman; J C Gutierrez-Ramos; C R Mackay Journal: J Clin Invest Date: 1996-02-01 Impact factor: 14.808
Authors: Nori Nagai; Meihua Ju; Kanako Izumi-Nagai; Scott J Robbie; James W Bainbridge; David C Gale; Esaie Pierre; Achim H P Krauss; Peter Adamson; David T Shima; Yin-Shan Ng Journal: Am J Pathol Date: 2015-07-16 Impact factor: 4.307