Cytokine-regulation of HIV-1 transcription in monocytes. Cytokines play an integral role in regulating the availability and activity of transcription factors that regulate the LTR. TNFα strongly induces the nuclear localization of NF-κB in monocytes. As a result, the subsequently stimulated LTR interfaces with increased levels of Sp and NF-κB factors. Cellular activation increases the expression of C/EBP, particularly activation by IL-6. TNF-α, IL-1, and interferon-γ reduce the expression of C/EBPα and increase expression of both C/EBPβ and C/EBPδ. Stimulation increases the expression of AP-1 in the cell where its interaction with NF-κB at the enhancer element leads to synergistic activation of the LTR. (Black arrows: translocation to nucleus; red arrows: decrease in expression; green arrows: increase in expression).