MMP-9 Upregulation is Attenuated by the Monoclonal TLR2 Antagonist T2.5 After Oxygen-Glucose Deprivation and Reoxygenation in Rat Brain Microvascular Endothelial Cells

大鼠脑微血管内皮细胞中氧-糖剥夺和复氧后,单克隆 TLR2 拮抗剂 T2.5 减弱了 MMP-9 的上调

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作者:Hongyan Zhu, Rongrong Dai, Hao Fu, Qiang Meng

Background

Blood-brain barrier (BBB) disruption plays a key role in the pathophysiology of acute ischemic stroke. Matrix metalloproteinases-2/9 (MMP-2/9) have been shown to participate in the disruption of the BBB and hemorrhagic transformation after cerebral ischemia. Toll-like receptor 2 (TLR2) may also be correlated with endothelial cell injury during ischemia-reperfusion events. However, the correlation between MMP-2/9 and TLR2 on endothelial cells after ischemia has not yet been evaluated. The

Conclusion

TLR2 antagonist T2.5 is able to downregulate the expression of MMP-9, and may constitute a therapeutic option for restoration of the BBB after OGDR.

Methods

Rat primary brain microvascular endothelial cells (BMECs) were cultured. Quantitative real-time PCR and western blotting were used to measure the mRNA and proteins expression of TLR2 and MMP-2/-9. The protein expression of TJs was detected by western blotting and immunofluorescence.

Results

MMP-9 significantly increased after OGDR. Protein and mRNA expression of TLR2 was also upregulated. However, claudin-5, occludin, collagen-Ⅳ, and ZO-1 were decreased after OGDR. When monoclonal anti-TLR2 antibody (T2.5) was added to BMECs after OGDR, MMP-9 was significantly downregulated, whereas occludin and collagen-Ⅳ had a tendency to increase.

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