Differential induction of PD-1/PD-L1 in Neuroimmune cells by drug of abuse.
Interaction of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) plays a critical role in regulating the delicate balance between protective immunity and tolerance. Human neuroimmune cells express very low or undetectable levels of PD-1/PD-L1 in normal physiological condition.We seek to examine if exposure of these cells to drug of abuse such as methamphetamine (METH) alters the profile of PD-1/PD-L1 levels, thereby dampens the innate immune response of the host cells. Thus, we assessed the changes in the levels of PD-1/PD-L1 in primary human macrophages, brain endothelial cells (hBECs), astrocytes, microglia, and neurons after exposure to METH. We observed that stimulation of these neuroimmune cells by METH responded differentially to PD-1/PD-L1 expression. Stimulation of macrophage culture with 50 μM of METH exhibited immediate gradual upregulation of PD-L1, while increase in PD-1 took 2-4 hours later than PD-L1. The response of hBECs to PD-1/PD-L1 induction occurred at 24 hours, while increase of PD-1/PD-L1 levels in neurons and microglia was immediate following METH exposure. We found that astrocytes expressed moderate levels of endogenous PD-1/PD-L1, which was diminished by METH exposure. Our findings show a differential expression of PD-1/PD-L1 in neuroimmune cells in response to METH stimulation, suggesting that PD-1/PD-L1 interplay in these cell types could orchestrate the intercellular interactive communication for neuronal death or protection in the brain environment.
Department of Biomedical Engineering, Center for Injury Bio Mechanics, Materials and Medicine, New Jersey Institute of Technology Newark, NJ 07102.
Vikas
V
Mishra
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha, NE 68198, USA.
Heather
H
Schuetz
Department of Biomedical Engineering, Center for Injury Bio Mechanics, Materials and Medicine, New Jersey Institute of Technology Newark, NJ 07102.
James
J
Haorah
Methamphetamine; neurodegeneration; neuroimmune cells; neuroinflammation; programmed cell death 1