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IL ‐1alpha induces angiogenesis in brain endothelial cells in vitro : implications for brain angiogenesis after acute injury
Author(s) -
Salmeron Kathleen,
Aihara Takuma,
RedondoCastro Elena,
Pinteaux Emmanuel,
Bix Gregory
Publication year - 2016
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 - 10.1111/jnc.13422
Subject(s) - angiogenesis , inflammation , endothelial stem cell , cytokine , endothelium , mediator , chemokine , cancer research , immunology , biology , medicine , microbiology and biotechnology , in vitro , pharmacology , biochemistry
Inflammation is a major contributor to neuronal injury and is associated with poor outcome after acute brain injury such as stroke. The pro‐inflammatory cytokine interleukin ( IL )‐1 is a critical regulator of cerebrovascular inflammation after ischemic injury, mainly through action of both of its isoforms, IL ‐1α and IL ‐1β, at the brain endothelium. In contrast, the differential action of these ligands on endothelial activation and post‐stroke angiogenesis is largely unknown. Here, we demonstrate that IL ‐1α is chronically elevated in the brain after experimental stroke suggesting that it is present during post‐stroke angiogenic periods. Furthermore, we demonstrate that IL ‐1α is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells in vitro . Using brain endothelial cell lines, we found that IL ‐1α was significantly more potent than IL ‐1β at inducing endothelial cell activation, as measured by expression of the pro‐angiogenic chemokine CXCL ‐1. IL ‐1α also induced strong expression of the angiogenic mediator IL ‐6 in a concentration‐dependent manner. Furthermore, IL ‐1α induced significant proliferation and migration of endothelial cells, and promoted formation of tube‐like structures that are established key hallmarks of angiogenesis in vitro . Finally, all of those responses were blocked by the IL ‐1 receptor antagonist ( IL ‐1 RA ). In conclusion, our data highlights a potential new role for IL ‐1 in brain repair mechanisms and identifies IL ‐1α as a potential new therapy to promote post‐stroke angiogenesis.Inflammation is a major contributor to neuronal injury and is associated with poor outcome after neurotrauma. We demonstrate that cytokine IL‐1α is chronically elevated in the brain after experimental stroke suggesting that it is present chronically post‐stroke. We demonstrate that IL‐1α is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells. Our data highlights a new role for IL‐1 in brain repair mechanisms and identifies IL‐1α as a potential therapy to promote post‐stroke angiogenesis.