Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells.
OBJECTIVE
Our previous studies revealed upregulation of stanniocalcin-1 (STC1) in cardiac vessels in dilated cardiomyopathy. However, the functional significance of STC1 is unknown. The objective of this study was to determine the effects of STC1 on TNF-alpha-induced monolayer permeability of human coronary artery endothelial cells (HCAECs).


RESULTS
Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF-alpha (2 ng/mL) for 24 hours. Monolayer permeability was studied using a transwell system. STC1 pretreatment significantly blocked TNF-alpha-induced monolayer permeability in a concentration- and time-dependent manner. STC1 effectively blocked TNF-alpha-induced downregulation of endothelial tight junction proteins zonula occluden-1 and claudin-1 at both mRNA and protein levels. STC1 also significantly decreased TNF-alpha-induced superoxide anion production. The inhibitory effect of STC1 was specific to TNF-alpha, as it failed to inhibit VEGF-induced endothelial permeability. Furthermore, STC1 partially blocked NF-kappaB and JNK activation in TNF-alpha-treated endothelial cells. JNK inhibitor and antioxidant also effectively blocked TNF-alpha-induced NF-kappaB activation and monolayer permeability in HCAECs.


CONCLUSIONS
STC1 maintains endothelial permeability in TNF-alpha-treated HCAECs through preservation of tight junction protein expression, suppression of superoxide anion production, and inhibition of the activation of NFkappaB and JNK, suggesting an important role for STC1 in regulating endothelial functions during cardiovascular inflammation.
Chen
Changyi
C
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex. 77030, USA. jchen@bcm.tmc.edu
Jamaluddin
Md Saha
MS
Yan
Shaoyu
S
Sheikh-Hamad
David
D
Yao
Qizhi
Q
D002121:Calcium Channel Blockers / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D062445:Claudin-1; D003331:Coronary Vessels / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D062826:Zonula Occludens-1 Protein
C568108:CLDN1 protein, human; D002121:Calcium Channel Blockers; D062445:Claudin-1; D006023:Glycoproteins; D008565:Membrane Proteins; D016328:NF-kappa B; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C569042:TJP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D062826:Zonula Occludens-1 Protein; D013481:Superoxides; C051795:teleocalcin; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D009543:Nifedipine