Alcohol induces programmed death receptor-1 and programmed death-ligand-1 differentially in neuroimmune cells

Vikas Mishra, Agnieszka Agas, Heather Schuetz, Jagathi Kalluru, James Haorah

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalAlcohol
Volume86
DOIs
StatePublished - Aug 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Keywords

  • EtOH
  • Neuroinflammation and Neurodegeneration
  • PD-1
  • PD-L1
  • Th1/Th2

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