Molecular mechanisms of IL-4 effect on HIV expression in promonocytic cell lines and primary human monocytes.
HIV-1 can productively infect mononuclear phagocytes derived from blood, bone marrow, brain, and lung. Interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha) have previously been shown to stimulate HIV replication in monocytes and macrophages. The mechanism of IL-4 stimulation was investigated and compared with the known effects of TNF-alpha. IL-4 up-regulated the expression of HIV mRNA within the first 2 days after infection of promonocytic U-937 cells and 3 to 4 days after infection of plastic-adherent blood macrophages with HIV-1. TNF-alpha also up-regulated production of HIV RNA but to a greater degree than IL-4, reaching a peak 3-4 days after addition. Northern blot analyses showed an increase in genomic and spliced RNAs at these times. However, there was reduced stimulation of HIV mRNA production when IL-4 and TNF-alpha were combined. These techniques are being used to further elucidate the mechanism of action of cytokines that inhibit HIV replication in purified human monocytes and macrophages.
Naif
H
H
Department of Virology, Westmead Hospital, Australia.
Ho-Shon
M
M
Chang
J
J
Cunningham
A L
AL
D015152:Blotting, Northern; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000737:chemistry / Q000166:cytology* / Q000382:microbiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000382:microbiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4