Alcohol induces programmed death receptor-1 and programmed death-ligand-1 differentially in neuroimmune cells.
Alcohol
; 86: 65-74, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32224220
ABSTRACT
Engagement of programmed death-1 (PD-1) receptor by its ligands (PD-L1/PD-L2) in activated immune cells is known to be involved in inflammatory neurological disease via a co-inhibitory signal pathway. Interaction of PD-1/PD-L1 is believed to occur only in activated neuroimmune cells because there are undetectable levels of PD-1/PD-L1 in normal physiological conditions. Here, we evaluated whether activation of neuroimmune cells such as human macrophage, brain endothelial cells (hBECs), astrocytes, microglia, and neurons by non-toxic concentrations of ethanol (EtOH) exposure can alter PD-1/PD-L1 expression. Thus, the present study is limited to the screening of PD-1/PD-L1 alterations in neuroimmune cells following ethanol exposure. We found that exposure of human macrophage or microglia to EtOH in primary culture immediately increased the levels of PD-L1 and gradually up-regulated PD-1 levels (beginning at 1-2 h). Similarly, ethanol exposure was able to induce PD-1/PD-L1 levels in hBECs and neuronal culture in a delayed process (occurring at 24 h). Astrocyte culture was the only cell type that showed endogenous levels of PD-1/PD-L1 that was decreased by EtOH exposure time-dependently. We concluded that ethanol (alcohol) mediated the induction of PD-1/PD-L1 differentially in neuroimmune cells. Taken together, our findings suggest that up-regulation of PD-1/PD-L1 by chronic alcohol use may dampen the innate immune response of neuroimmune cells, thereby contributing to neuroinflammation and neurodegeneration.
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Base de dados:
MEDLINE
Assunto principal:
Etanol
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Proteína 2 Ligante de Morte Celular Programada 1
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Receptor de Morte Celular Programada 1
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Neurônios
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article