κ opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression

Chun C. Chao, Genya Gekker, Shuxian Hu, Wen Sheng, Katherine B. Shark, Ding Fang Bu, Sydney Archer, Jean M. Bidlack, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Microglial cells, the resident macrophages of the brain, play an important role in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of κ opioid receptors (KORs) in human fetal microglia and inhibition of HIV- 1 expression in acutely infected microglial cell cultures treated with KOR ligands. Using reverse transcriptase-polymerase chain reaction and sequencing analyses, we found that mRNA for the KOR was constitutively expressed in microglia and determined that the nucleotide sequence of the open reading frame was identical to that of the human brain KOR gene. The expression of KOR in microglial cells was confirmed by membrane binding of [3H]U69,593, a κ-selective ligand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1 SF162 strain. This antiviral effect of the κ ligands was blocked by the specific KOR antagonist, nor-binaltrophimine. These findings suggest that κ opioid agonists have immunomodulatory activity in the brain, and that these compounds could have potential in the treatment of HIV-1-associated encephalopathy.

Original languageEnglish (US)
Pages (from-to)8051-8056
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number15
DOIs
StatePublished - Jul 23 1996

Keywords

  • U50,488
  • U69,593

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