RT Journal Article
SR Electronic
T1 Varicella zoster virus–infected cerebrovascular cells produce a proinflammatory environment
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e382
DO 10.1212/NXI.0000000000000382
VO 4
IS 5
A1 Jones, Dallas
A1 Neff, C. Preston
A1 Palmer, Brent E.
A1 Stenmark, Kurt
A1 Nagel, Maria A.
YR 2017
UL http://nn.neurology.org/content/4/5/e382.abstract
AB Objective: To test whether varicella zoster virus (VZV) infection of human brain vascular cells and of lung fibroblasts directly increases proinflammatory cytokine levels, consistent with VZV as a causative agent in intracerebral VZV vasculopathy and giant-cell arteritis (GCA).Methods: Conditioned supernatant from mock- and VZV-infected human brain vascular adventitial fibroblasts (HBVAFs), human perineurial cells (HPNCs), human brain vascular smooth muscle cells (HBVSMCs), and human fetal lung fibroblasts (HFLs) were collected at 72 hours postinfection and analyzed for levels of 30 proinflammatory cytokines using the Meso Scale Discovery Multiplex ELISA platform.Results: Compared with mock infection, VZV infection led to significantly increased levels of the following: interleukin-8 (IL-8) in all cell lines examined; IL-6 in HBVAFs, HPNCs, and HFLs, with no change in HBVSMCs; and vascular endothelial growth factor A in HBVAFs, HBVSMCs, and HFLs, with a significant decrease in HPNCs. Other cytokines, including IL-2, IL-4, IL-15, IL-16, TGF-b, Eotaxin-1, Eotaxin-3, IP-10, MCP-1, and granulocyte macrophage colony-stimulating factor, were also significantly altered upon VZV infection in a cell type–specific manner.Conclusions: VZV infection of vascular cells can directly produce a proinflammatory environment that may potentially lead to prolonged arterial wall inflammation and vasculitis. The VZV-mediated increase in IL-8 and IL-6 is consistent with that seen in the CSF of patients with intracerebral VZV vasculopathy, and the VZV-mediated increase in IL-6 is consistent with the cytokine's elevated levels in temporal arteries and plasma of patients with GCA.α-SMA=alpha–smooth muscle actin; BBB=blood-brain barrier; FBS=fetal bovine serum; FACS=fluorescence-activated cell sorting; GCA=giant-cell arteritis; GM-CSF=granulocyte macrophage colony-stimulating factor; HBVAF=human brain vascular adventitial fibroblast; HBVSMC=human brain vascular smooth muscle cell; HFL=human fetal lung fibroblast; HPNC=human perineurial cell; IFNγ=interferon gamma; IL=interleukin; TARC=thymus and activation-regulated chemokine; TNF-α=tumor necrosis factor alpha; TNF-β=tumor necrosis factor beta; TGF-β=transforming growth factor β; VZV=varicella zoster virus; VEGF-A=vascular endothelial growth factor A