Journal Article

Neuregulin1-β Decreases IL-1β-Induced Neutrophil Adhesion to Human Brain Microvascular Endothelial Cells

Leung, Wendy, Wu, Jiang, Lok, Josephine, Sykes, David B., Walas, Samantha, Wu, Limin, Lo, Eng H.

2015

Overview

Neuroinflammation contributes to the pathophysiology of diverse diseases including stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, resulting in neurodegeneration and loss of neurological function. The response of the microvascular endothelium often contributes to neuroinflammation. One such response is the upregulation of endothelial adhesion molecules which facilitate neutrophil adhesion to the endothelium and their migration from blood to tissue. Neuregulin-1 (NRG1) is an endogenous growth factor which has been reported to have anti-inflammatory effects in experimental stroke models. We hypothesized that NRG1 would decrease the endothelial response to inflammation and result in a decrease in neutrophil adhesion to endothelial cells. We tested this hypothesis in an in vitro model of cytokine-induced endothelial injury, in which human brain microvascular endothelial cells (BMECs) were treated with IL-1β, along with co-incubation with vehicle or NRG1-β. Outcome measures included protein levels of endothelial ICAM-1, VCAM-1, and E-selectin, as well as the number of neutrophils that adhere to the endothelial monolayer. Our data show that NRG1-β decreased the levels of VCAM-1, E-selectin, and neutrophil adhesion to brain microvascular endothelial cells activated by IL1-β. These findings open new possibilities for investigating NRG1 in neuroprotective strategies in brain injury.

• Publisher: Springer US,Springer Nature B.V
• Subject: Analysis of Variance / Animals / Biomedical and Life Sciences / Biomedicine / Brain - anatomy & histology / Cardiology / Cell Adhesion - drug effects / Cell death / Cells, Cultured / Cytokines / Cytotoxicity / Dose-Response Relationship, Drug / E-Selectin - metabolism / Endothelial Cells - drug effects / Endothelium / Endothelium, Vascular - cytology / Experiments / Female / Humans / Intercellular Adhesion Molecule-1 - metabolism / Interleukin-1beta - pharmacology / L-Lactate Dehydrogenase - metabolism / Laboratory animals / Leukocytes / Metabolism / Mice / Microscopy / Neuregulin-1 - pharmacology / Neurology / Neurosciences / Neurosurgery / Neutrophils / Neutrophils - drug effects / Neutrophils - physiology / Original Article / Proteins / Statistical analysis / Time Factors / Traumatic brain injury / Vascular Cell Adhesion Molecule-1 - metabolism / Vascular Surgery