TY - JOUR
T1 - Interleukin-10 induces inhibitory C/EBPβ through STAT-3 and represses HIV-1 transcription in macrophages
AU - Tanaka, Naohiko
AU - Hoshino, Yoshihiko
AU - Gold, Jeffrey
AU - Hoshino, Satomi
AU - Martiniuk, Frank
AU - Kurata, Takeshi
AU - Pine, Richard
AU - Levy, David
AU - Rom, William N.
AU - Weiden, Michael
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
KW - Infection
KW - Innate immunity
KW - Repression
KW - Transcription factors
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U2 - 10.1165/rcmb.2005-0140OC
DO - 10.1165/rcmb.2005-0140OC
M3 - Article
C2 - 16014896
AN - SCOPUS:26244441377
VL - 33
SP - 406
EP - 411
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 4
ER -