期刊
VIROLOGY
卷 397, 期 1, 页码 130-138出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.10.036
关键词
MMP; TIMP; Tight junction proteins; ZO-1; Claudin-1; Meningoencephalitis; BBB; Astrocytes; Human brain microvascular endothelial cells; GM6001
类别
资金
- Hawaii Community Foundation [20050405]
- Research Centers in Minority Institutions Program [G12RR003061]
- Centers of Biomedical Research Excellence [P20RR018727]
- National Center for Research Resources, National Institutes of Health
Though compromised blood-brain barrier (BBB) is a pathological hallmark of WNV-associated neurological sequelae, underlying mechanisms are unclear. We characterized the expression of matrix metalloproteinases (MMP) in WNV-infected human brain microvascular endothelial cells (HBMVE) and human brain cortical astrocytes (HBCA), components of BBB and their role in BBB disruption. Expression of multiple MMPs was significantly induced in WNV-infected HBCA cells. Naive HBMVE cells incubated with the supernatant from WNV-infected HBCA cells demonstrated loss of tight junction proteins, which were rescued in the presence of MMP inhibitor, GM6001. Further, supernatant from WNV-infected HBCA cells compromised the in vitro BBB model integrity. Our data suggest astrocytes as one of the sources of MMP in the brain, which mediates BBB disruption allowing unrestricted entry of immune cells into the brain, thereby contributing to WNV neuropathogenesis. Because of the unavailability of WNV antivirals and vaccines, use of MMP inhibitors as an adjunct therapy to ameliorate WNV disease progression is warranted. (C) 2009 Elsevier Inc. All rights reserved.
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