Activation of brain endothelial cells by interleukin-1 is regulated by the extracellular matrix after acute brain injuiry

作者：Summers Lauren; Kangwantas Korakoch; Rodriguez Grande Beatriz; Denes Adam; Penny Jeffrey; Kielty Cay; Pinteaux Emmanuel^*

来源：Molecular and Cellular Neuroscience, 2013, 57: 93-103.

DOI：10.1016/j.mcn.2013.10.007

• Extracellular matrix
• Cerebrovasculature
• Endothelia
• Inflammation
• Interleukin
• Integrin
• Brain injury

The extracellular matrix (ECM) of the central nervous system (CNS) is essential for normal brain function, whilst ECM remodelling is associated with cerebrovascular inflammation driven by the cytolcine interleukin-1 (IL-1) after acute brain injury. The effect of ECM remodelling on endothelial activation during neuroinflammation remains unknown. Here we report that ECM remodelling in the cerebrovasculature critically regulates IL-1-induced endothelial cell activation after cerebral ischaemia; Expression levels of ECM molecules associated with the cerebrovasculature, namely fibeonectin (FN) and collagen IV (Col IV), strongly increased in brain blood vessels after middle cerebral artery occlusion (MCAo) in a time-dependent manner, reaching a peak of vascular expression 48 h after MCAo. In cultures, FN and Col IV (but also laminin-1 and fibrillin-1) promoted strong attachment of the GPNT endothelial cell line and primary rat brain endothelial cells, which was markedly inhibited by RGD (Arg-Gly-Asp) peptide, or specific integrin beta 1, alpha 4, alpha 5 and alpha v blockade. IL-1 beta-induced activation of extracellular-regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF kappa B), and synthesis of cytokine-induced neutrophil chemoattractant (CINC-1) were enhanced in cells plated onto ECM molecules, and these responses were inhibited by selective integrin blockade. Finally, increased ECM expression in vessels after MCAo was found associated with vinculin clustering, increased integrin beta 1 expression, and increased IL-1 receptor associated kinase-1 (IRAK-1) activity in endothelial cells and perivascular astrocytes. Therefore, our data indicate a novel function for the ECM in the regulation of cerebrovascular inflammation triggered by IL-1 during acute brain injury.

• 出版日期2013-11