ATF-2 regulates lipopolysaccharide-induced transcription in macrophage cells

• Published in: Biochemical and biophysical research communications 2009-07, Vol.385 (1), p.72-77
• Main Authors: Hirose, Noriyuki, Maekawa, Toshio, Shinagawa, Toshie, Ishii, Shunsuke
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 2 - genetics; Activating Transcription Factor 2 - metabolism; Animals; ATF-2; Cell Line; Gene Expression Regulation; HDAC; Histone Deacetylase 1; Histone Deacetylase Inhibitors; Histone Deacetylases - metabolism; Hydroxamic Acids - pharmacology; Lipopolysaccharides - immunology; LPS; Macrophages - immunology; Mice; p38; Phosphorylation; Promoter Regions, Genetic; Socs-3; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Toll-like receptors; Toll-Like Receptors - genetics; Transcription, Genetic
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.05.001

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.