ATP Induces Disruption of Tight Junction Proteins via IL-1 Beta-Dependent MMP-9 Activation of Human Blood-Brain Barrier In Vitro

Disruption of blood-brain barrier (BBB) follows brain trauma or central nervous system (CNS) stress. However, the mechanisms leading to this process or the underlying neural plasticity are not clearly known. We hypothesized that ATP/P2X7R signaling regulates the integrity of BBB. Activation of P2X7...

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Veröffentlicht in:Neural plasticity. - 1998. - 2016(2016) vom: 24., Seite 8928530
1. Verfasser: Yang, Fuxing (VerfasserIn)
Weitere Verfasser: Zhao, Kai, Zhang, Xiufeng, Zhang, Jun, Xu, Bainan
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Neural plasticity
Schlagworte:Journal Article Interleukin-1beta P2RX7 protein, human Purinergic P2X Receptor Antagonists Receptors, Purinergic P2X7 Tight Junction Proteins Adenosine Triphosphate 8L70Q75FXE MMP9 protein, human EC 3.4.24.35 Matrix Metalloproteinase 9
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520 |a Disruption of blood-brain barrier (BBB) follows brain trauma or central nervous system (CNS) stress. However, the mechanisms leading to this process or the underlying neural plasticity are not clearly known. We hypothesized that ATP/P2X7R signaling regulates the integrity of BBB. Activation of P2X7 receptor (P2X7R) by ATP induces the release of interleukin-1β (IL-1β), which in turn enhances the activity of matrix metalloproteinase-9 (MMP-9). Degradation of tight junction proteins (TJPs) such as ZO-1 and occludin occurs, which finally contributes to disruption of BBB. A contact coculture system using human astrocytes and hCMEC/D3, an immortalized human brain endothelial cell line, was used to mimic BBB in vitro. Permeability was used to evaluate changes in the integrity of TJPs. ELISA, Western blot, and immunofluorescent staining procedures were used. Our data demonstrated that exposure to the photoreactive ATP analog, 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP), induced a significant decrease in ZO-1 and occludin expression. Meanwhile, the decrease of ZO-1 and occludin was significantly attenuated by P2X7R inhibitors, as well as IL-1R and MMP antagonists. Further, the induction of IL-1β and MMP-9 was closely linked to ATP/P2X7R-associated BBB leakage. In conclusion, our study explored the mechanism of ATP/P2X7R signaling in the disruption of BBB following brain trauma/stress injury, especially focusing on the relationship with IL-1β and MMP-9 
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650 7 |a Tight Junction Proteins  |2 NLM 
650 7 |a Adenosine Triphosphate  |2 NLM 
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700 1 |a Zhao, Kai  |e verfasserin  |4 aut 
700 1 |a Zhang, Xiufeng  |e verfasserin  |4 aut 
700 1 |a Zhang, Jun  |e verfasserin  |4 aut 
700 1 |a Xu, Bainan  |e verfasserin  |4 aut 
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