ATF-2 regulates lipopolysaccharide-induced transcription in macrophage cells

Biochem Biophys Res Commun. 2009 Jul 17;385(1):72-7. doi: 10.1016/j.bbrc.2009.05.001. Epub 2009 May 5.


The transcription factor ATF-2, a member of the ATF/CREB family, is a target of p38 that are involved in stress-induced apoptosis and in Toll-like receptor (TLR)-mediated signaling. Phosphorylation of ATF-2 at Thr-71 was enhanced by treating of RAW264.7 macrophage cells with either LPS, MALP-2, or CpG-ODN. LPS treatment enhanced the trans-activation capacity of ATF-2. Among multiple LPS-induced genes, the LPS-induced expression of Socs-3 was significantly reduced by the treatment of RAW264.7 cells with an Atf-2 siRNA. Transcription from the Socs-3 promoter was synergistically stimulated by ATF-2 and LPS, whereas it was suppressed by Atf-2 siRNA. Histone deacetylase 1 (HDAC1) interacted with ATF-2 after LPS treatment, but not before treatment. Treatment of RAW264.7 cells with trichostatin A, an inhibitor of HDAC, suppressed the LPS-induced Socs-3 expression, suggesting that HDAC1 positively regulates the LPS-induced transcription of Socs-3. Thus, ATF-2 plays an important role in TLR-mediated transcriptional control in macrophage cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / genetics
  • Activating Transcription Factor 2 / metabolism*
  • Animals
  • Cell Line
  • Gene Expression Regulation*
  • Histone Deacetylase 1
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism
  • Hydroxamic Acids / pharmacology
  • Lipopolysaccharides / immunology
  • Macrophages / immunology*
  • Mice
  • Phosphorylation
  • Promoter Regions, Genetic
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Toll-Like Receptors / genetics*
  • Transcription, Genetic


  • Activating Transcription Factor 2
  • Atf2 protein, mouse
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Lipopolysaccharides
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Toll-Like Receptors
  • trichostatin A
  • Hdac1 protein, mouse
  • Histone Deacetylase 1
  • Histone Deacetylases