The production of IL-10, which counteracts the effect of pro-inflammatory cytokines such as TNF-alpha, is induced by HIV-1 Tat in monocytes/macrophages by a process regulated by CREB-1 transcription factors . IL-10 has been reported to suppress HIV-1 replication in macrophages by inhibiting HIV-1 transcription  at a, but it has also been reported to contribute to cell-mediated immunity in the setting of HIV infection . We compared Tat-induced expression of IL-10 by THP-1 monocytes at 3% O2 (20 mmHg), the tension that monocytes see in certain tissues, and atmospheric 21% O2 (150 mmHg), the conventional in vitro culture condition. THP-1 cells were treated with recombinant HIV-Tat protein in combination with or without lipopolysaccharide (LPS) and IL-10 expression was analyzed by RT-PCR and ELISA. Treatment of THP-1 cells with HIV-Tat and LPS resulted in a dose- and time-dependent increase in IL-10 expression in the cells cultured at 21% O2. In contrast under 3% O2 the expression of IL-10 was reduced by 3-fold. Treatment with tautomycin, a protein phosphatase-1 (PP1) inhibitor, prevented IL-10 expression in LPS-stimulated THP-1 cells cultured at 21% O2. Thus, PP1 is likely to participate in Tat-mediated IL-10 production. PP1 has shown to affect CREB activity ; therefore we propose that PP1 might be involved in the CREB-mediated IL-10 gene expression. The inability of Tat to induce IL-10 production under 3% O2 might reflect the inadequate response of HIV-1 infected macrophages in vivo that might permit viral replication in infected macrophages. Further investigation of the role of PP1 in IL-10 expression could lead to new therapeutic opportunities for HIV-1 infection.
Disclosure: No relevant conflicts of interest to declare.