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Tumour necrosis factor alpha inhibits purinergic calcium signalling in blood–brain barrier endothelial cells
Author(s) -
Vandamme Wouter,
Braet Katleen,
Cabooter Liesbet,
Leybaert Luc
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02163.x
Subject(s) - connexin , purinergic receptor , gap junction , microbiology and biotechnology , paracrine signalling , calcium in biology , calcium , tumor necrosis factor alpha , biology , calcium signaling , cytokine , blood–brain barrier , endothelial stem cell , medicine , signal transduction , intracellular , endocrinology , immunology , biochemistry , extracellular , in vitro , receptor , central nervous system
The breaching of the blood–brain barrier is an essential aspect in the pathogenesis of neuroinflammatory diseases, in which tumour necrosis factor alpha (TNF‐α) as well as endothelial calcium ions play a key role. We investigated whether TNF‐α could influence the communication of calcium signals between brain endothelial cells (GP8 and RBE4). Intercellular calcium waves triggered by mechanical stimulation or photoliberation of InsP 3 in single cells were significantly reduced in size after TNF‐α exposure (1000 U/mL, 2 and 24 h). Calcium signals are communicated between cells by means of gap junctional and paracrine purinergic signalling. TNF‐α significantly inhibited gap junctional coupling, stimulated the basal release of ATP, and dose‐dependently blocked the triggered component of ATP release. The cytokine displayed similar effects on the uptake of a fluorescent reporter dye into the cells. Previous work with connexin mimetic peptides demonstrated that the triggered ATP release in these cells is connexin‐related; these peptides did, however, not influence the elevated basal ATP release caused by TNF‐α. We conclude that TNF‐α depresses calcium signal communication in blood–brain barrier endothelial cells, by reducing gap junctional coupling and by inhibiting triggered ATP release. The cytokine thus inhibits connexin‐related communication pathways like gap junctions and connexin hemichannels.