title: Neuregulin1-β decreases IL-1β-induced neutrophil adhesion to human brain microvascular endothelial cells.
abstract: 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.
authors.affiliation: Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Limin
authors.initials: L
authors.lastname: Wu
authors.forename: Samantha
authors.initials: S
authors.lastname: Walas
authors.forename: Wendy
authors.initials: W
authors.lastname: Leung
authors.forename: David B
authors.initials: DB
authors.lastname: Sykes
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Josephine
authors.initials: J
authors.lastname: Lok
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D020890:Neuregulin-1 / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019040:E-Selectin; D053583:Interleukin-1beta; D020890:Neuregulin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase