Alcohol induces programmed death receptor-1 and programmed death-ligand-1 differentially in neuroimmune cells
Document Type
Article
Publication Date
8-1-2020
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.
Identifier
85084522752 (Scopus)
Publication Title
Alcohol
External Full Text Location
https://doi.org/10.1016/j.alcohol.2020.03.009
e-ISSN
18736823
ISSN
07418329
PubMed ID
32224220
First Page
65
Last Page
74
Volume
86
Grant
R21AA022734
Fund Ref
National Institutes of Health
Recommended Citation
Mishra, Vikas; Agas, Agnieszka; Schuetz, Heather; Kalluru, Jagathi; and Haorah, James, "Alcohol induces programmed death receptor-1 and programmed death-ligand-1 differentially in neuroimmune cells" (2020). Faculty Publications. 5123.
https://digitalcommons.njit.edu/fac_pubs/5123
