Endogenous opioid peptides suppress cytokine-mediated upregulation of HIV-1 expression in the chronically infected promonocyte clone U1.
Opioid peptides appear to have an immunomodulatory activity. Using the chronically HIV-1-infected promonocyte clone U1, we investigated the effect of endogenous and synthetic opioid agonists on cytokine-induced HIV-1 expression. None of the endogenous or synthetic opioid agonists had an effect on constitutive HIV-1 expression. Opioid agonists such as methionine-enkephalin, dynorphin, and the kappa receptor agonist, U50,488, dose-dependently suppressed (> 40%) interleukin (IL)-6-induced upregulation of HIV-1 expression. Interestingly, opioid receptor antagonists (mu, delta, and kappa types) also inhibited (> 60%) IL-6-induced upregulation of HIV-1 expression. All opioid agonists and antagonists tested only modestly suppressed (< 20%) tumor necrosis factor-alpha-induced upregulation of HIV-1 expression in U1 cell cultures. These data suggest that certain opioid peptides alter an IL-6-induced signal transduction pathway which triggers HIV-1 expression in the chronically infected promonocyte U1.
Chao
C C
CC
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Gekker
G
G
Sheng
W S
WS
Hu
S
S
Portoghese
P S
PS
Peterson
P K
PK
D002999:Clone Cells; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism* / Q000821:virology*; D011957:Receptors, Opioid / Q000819:agonists; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D004723:Endorphins; D011957:Receptors, Opioid