HIV-1 gp120 up-regulation of the mu opioid receptor in TPA-differentiated HL-60 cells.
Opioid abuse has been shown to exacerbate the immunosuppressive effects and pathogenesis of HIV infection. The mu opioid receptor (MOR) is present on immune cells, such as macrophages, and mediates the direct immunomodulatory effects of opioids. Through its surface glycoprotein, gp120, HIV-1 binds to surface receptors on target cells, including macrophages, to exert its pathological effects. Binding of gp120 to macrophages stimulates the cells to release various pro-inflammatory cytokines, including TNF-alpha, which has been shown to regulate transcription of the MOR gene. In this study, we examined the effects of HIV-1 gp120 on MOR expression in HL-60 human promyelocytic leukemia cells differentiated into macrophage-like cells by TPA. Using real time RT-PCR, we found that exposure to gp120 up-regulated MOR expression in TPA-differentiated HL-60 cells at the transcriptional level. The functionality of the gp120-induced MOR in these cells was confirmed based on morphine's inhibition of forskolin-induced intracellular cAMP, which was naloxone reversible. Exposure to gp120 also stimulated the release of TNF-alpha from TPA-differentiated HL-60 cells. Treatment with TNF-alpha neutralizing antibody, as well as blockage of TNF-alpha's actions by anti-TNF-alpha receptor type II (TNFR-II) antibody, inhibited gp120-induced up-regulation of MOR mRNA. Our data suggest that one of the mechanisms by which HIV-1 gp120 up-regulates the MOR in TPA-differentiated HL-60 cells is through autocrine/paracrine actions of TNF-alpha via the TNFR-II receptor.
Beltran
Jose A
JA
Department of Biology, Seton Hall University, McNulty Hall, Room 215, South Orange, NJ 07079, USA.
Pallur
Anitha
A
Chang
Sulie L
SL
D002454:Cell Differentiation / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D017450:Receptors, Opioid, mu / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics
D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D013755:Tetradecanoylphorbol Acetate