KAPPA-OPIOID RECEPTORS IN HUMAN MICROGLIA DOWN-REGULATE HUMAN-IMMUNODEFICIENCY-VIRUS-1 EXPRESSION

Microglial cells, the resident macrophages of the brain, play an impor tant role in the neuropathogenesis of human immunodeficiency virus typ e 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of kappa opioid receptors (KORs) in human fetal microglia an d inhibition of HIV-1 expression in acutely infected microglial cell c ultures treated with KOR ligands, Using reverse transcriptase-polymera se 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 w as confirmed by membrane binding of [H-3]U69,593, a kappa-selective li gand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibit ion of expression of the monocytotropic HIV-1 SF162 strain, This antiv iral effect of the kappa ligands was blocked by the specific KOR antag onist, nor-binaltrophimine. These findings suggest that kappa opioid a gonists have immunomodulatory activity in the brain, and that these co mpounds could have potential in the treatment of HIV-1-associated ence phalopathy.