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Sepsis

Calming the cytokine storm

Nature Reviews Drug Discovery volume 9, pages 360–361 (2010)Cite this article

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The Slit family of neurovascular guidance cues inhibit vascular endothelial growth factor (VEGF)-induced vascular hyperpermeability in a process that is dependent on the endothelial-specific receptor ROBO4. So, the authors examined the effects of the active amino-terminal fragment of Slit (Slit2N) in cells and in vivo to determine whether ROBO4-dependent Slit signalling can stabilize vascular function.

In an in vitro model of vascular barrier function, Slit2N reduced lipopolysaccharide- and cytokine-induced permeability of human endothelial cell monolayers. Further studies using human microvascular lung endothelial cells demonstrated that Slit2N preserves cell–cell interactions under conditions of cytokine stimulation by reducing the endocytosis of the adherens junction protein vascular endothelial-cadherin.

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ORIGINAL RESEARCH PAPER

  1. London, N. R. et al. Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Science Transl. Med. 2, 23ra19 (2010)

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  1. Charlotte Harrison
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Harrison, C. Calming the cytokine storm. Nat Rev Drug Discov 9, 360–361 (2010). https://doi.org/10.1038/nrd3162

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