Interplay of inflammatory gene expression in pericytes following Japanese encephalitis virus infection.
Brain Behav Immun
; 66: 230-243, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28690034
ABSTRACT
Neuroinflammation is a pathological hallmark and has been implicated in the pathogenesis of Japanese encephalitis. Although brain pericytes show regulatory effects on neuroinflammation, their involvement in Japanese encephalitis-associated neuroinflammation is not understood. Here, we demonstrated that brain microvascular pericytes could be an alternative cellular source for the induction and/or amplification of neuroinflammation caused by Japanese encephalitis virus (JEV) infection. Infection of cultured pericytes with JEV caused profound production of IL-6, RANTES, and prostaglandin E2 (PGE2). Mechanistic studies revealed that JEV infection elicited an elevation of the toll-like receptor 7 (TLR7)/MyD88 signaling axis, leading to the activation of NF-κB through IKK signaling and p65 phosphorylation as well as cAMP response element-binding protein (CREB) via phosphorylation. We further demonstrated that extracellular signal-regulated kinase (ERK) could be an alternative regulator in transducing signals to NF-κB, CREB, and cytosolic phospholipase A2 (cPLA2) through the phosphorylation mechanism. Released IL-6 and RANTES played an active role in the disruption of endothelial barrier integrity and leukocyte chemotaxis, respectively. cPLA2/PGE2 had a role in activating NF-κB and CREB DNA-binding activities and inflammatory cytokine transcription via the EP2/cAMP/PKA mechanism in an autocrine loop. These inflammatory responses and biochemical events were also detected in the brain of JEV-infected mice. The current findings suggest that pericytes might have pathological relevance in Japanese encephalitis-associated neuroinflammation through a TLR7-related mechanism. The consequences of pericyte activation are their ability to initiate and/or amplify inflammatory cytokine expression by which cellular function of endothelial cells and leukocytes are regulated in favor of CNS infiltration by leukocytes.
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Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
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Encefalite Japonesa
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Mediadores da Inflamação
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Pericitos
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article