Tumor necrosis factor-? disruption of brain endothelial cell barrier is mediated through matrix metalloproteinase-9 - 02/12/14
Abstract |
Traumatic brain injuries cause vascular hyperpermeability. Tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and caspase-3 may be important in these processes but the relationship between them has not been investigated. We hypothesized that TNF-α regulates caspase-3-mediated hyperpermeability and blood brain barrier damage and hyperpermeability directly or indirectly via activation of MMP-9. To test this, rat brain microvascular endothelial cells were treated with TNF-α with or without inhibition of MMP-9. Monolayer permeability was measured, zonula occludens-1 and F-actin configuration were examined, and MMP-9 and caspase-3 activities were quantified. TNF-α increased monolayer permeability, damaged zonula occludens-1, induced filamentous-actin stress fiber formation, and increased both MMP-9 and caspase-3 activities. Inhibition of MMP-9 attenuated these changes. These data highlight a novel link between TNF-α and MMP-9 and show that TNF-α regulated caspase-3-mediated hyperpermeability and vascular damage may be linked to MMP-9 in vitro. These findings augment the understanding of traumatic brain injury and pave the way for improved treatment.
Le texte complet de cet article est disponible en PDF.Keywords : Traumatic brain injury, Blood brain barrier, Matrix metalloproteinase, Gelatinase B, Tumor necrosis factor, Caspase-3
Plan
The authors declare no conflicts of interest. |
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We acknowledge the Office of Academic Operations and Department of Surgery, Baylor Scott & White Health, Temple, Texas, for financial support and Texas A&M Health Science Center College of Medicine Integrated Imaging Laboratory for the use of the confocal laser microscope and technical assistance with imaging. |
Vol 208 - N° 6
P. 954-960 - décembre 2014 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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