Differential induction of PD-1/PD-L1 in neuroimmune cells by drug of abuse

Vikas Mishra, Heather Schuetz, James Haorah

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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/PDL1 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.

Original languageEnglish (US)
Pages (from-to)87-97
Number of pages11
JournalInternational Journal of Physiology, Pathophysiology and Pharmacology
Volume7
Issue number2
StatePublished - Aug 18 2015

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Physiology
  • Physiology (medical)

Keywords

  • Methamphetamine
  • Neurodegeneration
  • Neuroimmune cells
  • Neuroinflammation
  • Programmed cell death 1

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