Upregulation of HIV-1 expression in cocultures of chronically infected promonocytes and human brain cells by dynorphin.
Using cocultures of human fetal brain cells and a chronically human immunodeficiency virus-1 (HIV-1)-infected promonocytic line U1, we investigated the effect of dynorphin, an endogenous opioid peptide found in the CNS, on upregulation of HIV-1 expression. Dynorphin and the synthetic kappa receptor agonist U50,488 promoted HIV-1 expression with a bell-shaped concentration-response relationship in which maximal effects were observed at 10(-13) and 10(-11) M, respectively. Pretreatment for 30 min with the kappa receptor antagonist nor-binaltorphimine completely blocked the stimulatory effect of dynorphin and U50,488. The involvement of cytokines on HIV-1 expression was tested. Dynorphin-induced upregulation of HIV-1 in the cocultures was largely blocked by antibodies to tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 but not by antibodies to IL-10. Also, dynorphin stimulated TNF-alpha and IL-6 in the brain cell cultures at both mRNA and protein levels, suggesting the involvement of these cytokines in opioid-induced HIV-1 expression. These findings suggest that endogenous opioid peptides such as dynorphin may have an immunomodulatory function in the CNS and could act as a cofactor in the neuropathogenesis of HIV-1.
Chao
C C
CC
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Gekker
G
G
Hu
S
S
Sheng
W S
WS
Portoghese
P S
PS
Peterson
P K
PK
D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D017931:DNA Primers; D004399:Dynorphins / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D017473:Receptors, Opioid, kappa / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects*
D017931:DNA Primers; D015850:Interleukin-6; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; D014409:Tumor Necrosis Factor-alpha; C026843:dynorphin (1-13); D004399:Dynorphins