Bluetongue Virus and Double-Stranded RNA Increase Human Vascular Permeability: Role of p38 MAPK

被引:0
|
作者
EDDIE T. CHIANG
DIXIE-ANN PERSAUD-SAWIN
SANDHYA KULKARNI
JOE G. N. GARCIA
FARHAD IMANI
机构
[1] NIEHS/NIH,
[2] Laboratory of Respiratory Biology,undefined
[3] University of Chicago,undefined
[4] Pritzker School of Medicine,undefined
[5] NIEHS/NIH MD 2-01,undefined
来源
Journal of Clinical Immunology | 2006年 / 26卷
关键词
hemorrhagic fever; vascular permeability; double-stranded RNA (dsRNA); bluetongue virus; MAP kinase;
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学科分类号
摘要
Endothelial cell (EC) involvement in viral hemorrhagic fevers has been clearly established. However, virally activated mechanisms leading to endothelial activation and dysfunction are not well understood. Several different potential mechanisms such as direct viral infection, alterations in procoagulant/anticoagulant balance, and increased cytokine production have been suggested. We utilized a model of EC barrier dysfunction and vascular endothelial leakage to explore the effect of bluetongue virus (BTV), a hemorrhagic fever virus of ruminants, on human lung endothelial cell barrier properties. Infection of human lung EC with BTV induced a significant and dose-dependent decrease in trans-endothelial electrical resistance (TER). Furthermore, decreases in TER occurred in conjunction with cytoskeletal rearrangement, suggesting a direct mechanism for viral infection-mediated endothelial barrier disruption. Interestingly, double-stranded RNA (dsRNA) mimicked the effects of BTV on endothelial barrier properties. Both BTV- and dsRNA-induced endothelial barrier dysfunction was blocked by treatment with a pharmacological inhibitor of p38 MAPK. The induction of vascular permeability by dsRNA treatment or BTV infection was concomitent with induction of inflammatory cytokines. Taken together, our data suggest that the presence of dsRNA during viral infections and subsequent activation of p38 MAPK is a potential molecular pathway for viral induction of hemorrhagic fevers. Collectively, our data suggest that inhibition of p38 MAPK may be a possible therapeutic approach to alter viral-induced acute hemorrhagic diseases.
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页码:406 / 416
页数:10
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