Interleukin-10 Induces Inhibitory C/EBPβ through STAT-3 and Represses HIV-1 Transcription in Macrophages

Pulmonary tuberculosis (TB) has been characterized by inflammation with increased pro- or anti-inflammatory cytokines produced by macrophages. We have reported that IFN produces inhibitory C/EBPβ and represses transcription of the HIV-1 LTR in macrophages. STAT-1 and type I IFN receptor knockout mice have macrophages that are defective in IFN signaling, yet LPS stimulation induces inhibitory C/EBPβ, demonstrating that other cytokines can induce this repressor. LPS or Mycobacterium tuberculosis–derived lipoarabinomannan induce the anti-inflammatory cytokine interleukin (IL)-10, which represses the HIV-1 LTR in differentiated THP-1 macrophages by inducing inhibitory C/EBPβ. In contrast, in undifferentiated THP-1 monocytes, IL-10 did not inhibit HIV-1 replication or induce C/EBPβ. IL-10 signal transduction uses STAT-3, and macrophages from STAT-3−/− mice fail to produce inhibitory C/EBPβ after LPS or IL-10 stimulation. Transfection of STAT-3 into THP-1 cells enhances C/EBPβ promoter activity. THP-1 different...