Interleukin-10 induces inhibitory C/EBPβ through STAT-3 and represses HIV-1 transcription in macrophages

Naohiko Tanaka, Yoshihiko Hoshino, Jeffrey Gold, Satomi Hoshino, Frank Martiniuk, Takeshi Kurata, Richard Pine, David Levy, William N. Rom, Michael Weiden

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 1 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 represser. 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 differentiation also increases STAT-3 protein, but not STAT-3 gene transcription, and induces a translational regulator, CUG-binding protein, that was essential for production of C/EBPβ. Differentiation induced post-transcriptional regulation is required to produce inhibitory C/EBPβ in response to IL-10. Only macrophages are able to repress HIV-1 LTR promoter activity and inhibit viral replication in response to IL-10 or type 1 IFN.

Original languageEnglish (US)
Pages (from-to)406-411
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Issue number4
StatePublished - Oct 2005
Externally publishedYes


  • Infection
  • Innate immunity
  • Repression
  • Transcription factors

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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