HIV-1 gp120 induces cytokine expression, leukocyte adhesion, and transmigration across the blood-brain barrier: modulatory effects of STAT1 signaling.
Microvasc Res
; 77(2): 212-9, 2009 Mar.
Article
en En
| MEDLINE
| ID: mdl-19103208
ABSTRACT
How neuroinflammatory activities affect signaling pathways leading to blood-brain barrier (BBB) injury during HIV/AIDS are currently unknown. Our previous work demonstrated that HIV-1 exposure activates pro-inflammatory genes in human brain microvascular endothelial cells (HBMEC) and showed that these genes are linked to the janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Here, we report that HIV-1 gp120 protein activated STAT1 and induced interleukin (IL)-6 and IL-8 secretion in HBMEC. IL-6, IL-8, and gp120 increased monocyte adhesion and migration across in vitro BBB models. The STAT1 inhibitor, fludarabine, prevented gp120-induced IL-6 and IL-8 secretion. Inhibitors of STAT1, mitogen activated protein kinase kinase (MEK) (PD98059), and phosphatidyl inositol 3 kinase (PI3K) (LY294002), blocked gp120-induced STAT1 activation and significantly diminished IL-8-, IL-6-, and gp120-induced monocyte adhesion and migration across in vitro BBB models. These data support the notion that STAT1 plays an important role in gp120-induced inflammation and BBB dysfunction associated with viral infection. Results also suggest crosstalk between STAT1, MEK, and PI3K pathways in gp120-induced BBB dysfunction. Inhibition of STAT1 activation could provide a unique therapeutic strategy to decrease neuroinflammation and BBB dysfunction in HIV/AIDS.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
/
Monocitos
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Proteína gp120 de Envoltorio del VIH
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Citocinas
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VIH-1
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Factor de Transcripción STAT1
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Microvasc Res
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos