δ-Opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat)

Burt Sharp, Genya Gekker, Ming D. Li, Chun C. Chao, Phillip K. Peterson

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

δ-opioid receptor (DOR) transcripts and binding sites are expressed by lymphocytes and lymphoid cell lines from several species. Direct modulation of lymphocyte function through DORs affects T cell proliferation, interleukin-2 production, chemotaxis, and intracellular signaling. Moreover, in human DOR-transfected T cells (DOR-Ju.1), δ-opioids have been shown previously to mobilize intracellular calcium rapidly, to inhibit forskolin-stimulated cyclic AMP production, and to activate the mitogen-activated protein kinases ERKs 1 and 2. These observations led us to consider whether δ agonists modify T cell functions, thus affecting the expression of human immunodeficiency virus-1 (HIV-1) by CD4+ T cells. To test this hypothesis, DOR-Ju.1 cells, derived from Jurkat cells stably transfected with a cDNA encoding the neuronal DOR, were stimulated with deltorphin or benzamide, 4-[[2,5-dimethyl-4-(2-propenyl)-1-piperazinyl](3-methoxyphenyl)methyl]N-,[2S[(S*),2α,5β]]-(9Cl) (SNC-80) prior to the addition of HIV-1. Both deltorphin and SNC-80 concentration-dependently inhibited the production of p24 antigen, an index of HIV-1 expression. Inhibition was maximal with 10-13-10-9 M SNC-80 (>60% reduction) or 10-15-10-11 M deltorphin (>50% reduction). At higher concentrations, less inhibition of p24 antigen production was found. Naltrindole (NTI, 10-11 M), a selective DOR antagonist, abolished the inhibitory effects of 10-9 M SNC-80, whereas 10-13 M NTI partially reversed the effect of SNC-80. Thus, activation of DORs expressed by CD4+ T cells significantly (P < 0.05) reduced the expression of HIV-1 by these cells. These findings suggest that opioid immunomodulation directed at host T cells may be adjunctive to standard antiviral approaches to HIV-1 infection. Copyright (C) 1998 Elsevier Science, Inc.

Original languageEnglish (US)
Pages (from-to)289-292
Number of pages4
JournalBiochemical Pharmacology
Volume56
Issue number3
DOIs
StatePublished - Aug 1 1998

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T-cells
Viruses
Opioid Analgesics
HIV-1
T-Lymphocytes
naltrindole
Lymphocytes
Antigens
Jurkat Cells
Immunomodulation
Mitogen-Activated Protein Kinase 1
Cell proliferation
Opioid Receptors
Colforsin
Virus Diseases
Chemotaxis
Mitogen-Activated Protein Kinases
Cyclic AMP
Interleukin-2
Antiviral Agents

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

δ-Opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat). / Sharp, Burt; Gekker, Genya; Li, Ming D.; Chao, Chun C.; Peterson, Phillip K.

In: Biochemical Pharmacology, Vol. 56, No. 3, 01.08.1998, p. 289-292.

Research output: Contribution to journalArticle

Sharp, Burt ; Gekker, Genya ; Li, Ming D. ; Chao, Chun C. ; Peterson, Phillip K. / δ-Opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat). In: Biochemical Pharmacology. 1998 ; Vol. 56, No. 3. pp. 289-292.
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