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Bradykinin receptor‐1 activation induces inflammation and increases the permeability of human brain microvascular endothelial cells
Author(s) -
Mugisho Odunayo O.,
Robilliard Laverne D.,
Nicholson Louise F. B.,
Graham E. Scott,
O'Carroll Simon J.
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11232
Subject(s) - occludin , inflammation , cytokine , vascular permeability , bradykinin , receptor , stimulation , blood–brain barrier , endocrinology , neuroinflammation , endothelial activation , medicine , vascular endothelial growth factor , cell adhesion molecule , evans blue , microbiology and biotechnology , biology , immunology , tight junction , central nervous system , vegf receptors
Neuroinflammatory disorders such as Alzheimer's and Parkinson's diseases are characterised by chronic inflammation and loss of vascular integrity. Bradykinin 1 receptor (B1R) activation has been implicated in many neuroinflammatory diseases, but the contribution of B1R to inflammation and vascular breakdown is yet to be determined. As a result, the present study evaluated the effect of B1R stimulation using Des‐Arg‐9‐BK on the cytokine profile and junctional properties of human cerebral microvascular endothelial cells (hCMVECs). Results showed that stimulation of B1R receptors increased secretion of pro‐inflammatory cytokines, interleukin‐6 (IL‐6), IL‐8, intracellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and monocyte chemoattractant protein‐1 (MCP‐1), but decreased the expression of vascular endothelial growth factor (VEGF), a cytokine and growth factor required for maintenance of the vasculature. B1R stimulation also resulted in the loss of occludin expression at tight junctions with no change in VE‐cadherin expression. There was also a significant increase in permeability to Evans blue albumin, suggesting an increase of vascular permeability. Taken together, these results suggest that B1R activation that occurs in neuroinflammatory diseases may contribute to both the inflammation and loss of blood‐brain barrier integrity that is characteristic of these diseases.