Compromised blood-brain barrier (BBB) by dysregulation of cellular junctions is a hallmark of many
cerebrovascular disorders due to the pro-inflammatory
cytokines action.
Interleukin 6 (
IL6) is implicated in inflammatory processes and in secondary
brain injury after
subarachnoid hemorrhage (SAH) but its role in the maintenance of cerebral endothelium still requires a precise elucidation. Although
IL6 has been shown to exert pro-inflammatory action on brain microvascular endothelial cells (ECs), the expression of one of the
IL6 receptors, the IL6R is controversially discussed. In attempt to reach more clarity in this issue, we present here an evident baseline expression of the IL6R in BBB endothelium in vivo and in an in vitro model of the BBB, the cEND cell line. A significantly increased expression of IL6R and its
ligand was observed in BBB capillaries 2 days after experimental SAH in mice. In vitro, we saw
IL6 administration resulting in an intracellular and extracellular elevation of
IL6 protein, which was accompanied by a reduced expression of tight and adherens junctions, claudin-5,
occludin, and vascular-endothelial (
VE-) cadherin. By functional assays, we could demonstrate IL6-incubated brain ECs to lose their endothelial integrity that can be attenuated by inhibiting the IL6R. Blockade of the IL6R by a
neutralizing antibody has reconstituted the intercellular junction expression to the control level and caused a restoration of the transendothelial electrical resistance of the cEND cell monolayer. Our findings add depth to the current understanding of the involvement of the endothelial IL6R in the loss of EC integrity implicating potential
therapy options.