Neuron-derived CCL2 contributes to microglia activation and neurological decline in hepatic encephalopathy
Biol. Res
; 50: 26, 2017. graf
Artigo
em Inglês
| LILACS
| ID: biblio-950876
Biblioteca responsável:
CL1.1
ABSTRACT
BACKGROUND:
CCL2 was up-regulated in neurons and involved in microglia activation and neurological decline in mice suffering from hepatic encephalopathy (HE). However, no data exist concerning the effect of neuron-derived CCL2 on microglia activation in vitro.METHODS:
The rats were pretreated with CCL2 receptor inhibitors (INCB or C021, 1 mg/kg/day i.p.) for 3 days prior to thioacetamide (TAA) administration (300 mg/kg/day i.p.) for inducing HE model. At 8 h following the last injection (and every 4 h after), the grade of encephalopathy was assessed. Blood and whole brains were collected at coma for measuring CCL2 and Iba1 expression. In vitro, primary neurons were stimulated with TNF-α, and then the medium were collected for addition to microglia cultures with or without INCB or C021 pretreatment. The effect of the medium on microglia proliferation and activation was evaluated after 24 h.RESULTS:
CCL2 expression and microglia activation were elevated in the cerebral cortex of rats received TAA alone. CCL2 receptors inhibition improved neurological score and reduced cortical microglia activation. In vitro, TNF-α treatment induced CCL2 release by neurons. Medium from TNF-α stimulated neurons caused microglia proliferation and M1 markers expression, including iNOS, COX2, IL-6 and IL-1ß, which could be suppressed by INCB or C021 pretreatment. The medium could also facilitate p65 nuclear translocation and IκBα phosphorylation, and NF-κB inhibition reduced the increased IL-6 and IL-1ß expression induced by the medium.CONCLUSION:
Neuron-derived CCL2 contributed to microglia activation and neurological decline in HE. Blocking CCL2 or inhibiting microglia excessive activation may be potential strategies for HE.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Contexto em Saúde:
Agenda de Saúde Sustentável para as Américas
Problema de saúde:
Objetivo 9: Redução de doenças não transmissíveis
Base de dados:
LILACS
Assunto principal:
Encefalopatia Hepática
/
Microglia
/
Quimiocina CCL2
/
Receptores de Quimiocinas
/
Neurônios
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Biol. Res
Assunto da revista:
Biologia
Ano de publicação:
2017
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
The Second People's Hospital of Lanzhou/CN