Schroder, Kate and Lichtinger, Monika and Irvine, Katharine M. and Brion, Kristian and Trieu, Angela and Ross, Ian L. and Ravasi, Timothy and Stacey, Katryn J. and Rehli, Michael and Hume, David A. and Sweet, Matthew J. (2007) PU.1 and ICSBP control constitutive and IFN-gamma-regulated Tlr9 gene expression in mouse macrophages. JOURNAL OF LEUKOCYTE BIOLOGY, 81 (6). pp. 1577-1590. ISSN 0741-5400,
Full text not available from this repository. (Request a copy)Abstract
Macrophages are activated by unmethylated CpG-containing DNA (CpG DNA) via TLR9. IFN-gamma and LPS can synergize with CpG DNA to enhance proinflammatory responses in murine macrophages. Here, we show that LPS and IFN-gamma up-regulated Tlr9 mRNA in murine bone marrow-derived macrophages (BMM). The ability of LPS and IFN-gamma to induce Tlr9 mRNA expression in BMM was dependent on the presence of the growth factor, CSF-1, which is constitutively present in vivo. However, there were clear differences in mechanisms of Tlr9 mRNA induction. LPS stimulation rapidly removed the CSF-1 receptor (CSF-IR) from the cell surface, thereby blocking CSF-1-mediated transcriptional repression and indirectly inducing Tlr9 mRNA expression. By contrast, IFN-gamma activated the Tlr9 promoter directly and only marginally affected cell surface CSF-1R expression. An similar to 100-bp proximal promoter of the murine Tlr9 gene was sufficient to confer basal and IFN-,gamma-inducible expression in RAW264.7 cells. A composite IFN regulatory factor (IRF)/PU.1 site upon the major transcription start site was identified. Mutation of the binding sites for PU.1 or IRF impaired basal promoter activity, but only the IRF-binding site was required for IFN-gamma induction. The mRNA expression of the IRF family member IFN consensus-binding protein [(ICSBP)/IRF8] was coregulated with Tlr9 in macrophages, and constitutive and IFN-gamma-inducible Tlr9 mRNA expression was reduced in ICSBP-deficient BMM. This study therefore characterizes the regulation of mouse Tlr9 expression and defines a molecular mechanism by which IFN-gamma amplifies mouse macrophage responses to CpG DNA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SEQUENCE-BINDING-PROTEIN; TOLL-LIKE RECEPTOR-9; PLASMACYTOID DENDRITIC CELLS; MURINE PERITONEAL-MACROPHAGES; STIMULATED RESPONSE ELEMENT; BACTERIAL CPG-DNA; NF-KAPPA-B; INTERFERON-GAMMA; TRANSCRIPTIONAL-REGULATION; CUTTING EDGE; colony-stimulating factor-1; inflamination; lipopolysaccharide; interferon; IRF8; Toll-like receptor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Dec 2020 09:23 |
| Last Modified: | 04 Dec 2020 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32686 |
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