PU.1 and ICSBP control constitutive and IFN-gamma-regulated Tlr9 gene expression in mouse macrophages

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

Annual program review, forest biology, October 14-15, 1998

"October 14-15, 1998."Mass clonal propagation of improved conifers: project F010 / Jerry Pullman ... [et al.] ; Mass clonal propagation of improved conifers - initiation / Gerald Pullman ... [et al.] ; Mass clonal propagation of improved conifers: genetic control of initiation and the number of zygotic embryos in the seed / John MacKay ... [et al.] ; Mass clonal propagation of improved conifers: survival of initiated cultures after direct transfer to liquid media / Gary Peter ... [et al.] ; Mass clonal propagation of improved conifers - embryo development improvements based on elemental analysis of female gametophyte, zygotic and somatic embryo tissues / Gerald Pullman, Paul Montello, Xiaorong Feng ; Mass clonal propagation of improved conifers: optimizing the percent of embryos that develop into cotyledonary embryos by altering embryo plating densities and ABA concentration / Teresa Vales, Gary Peter ; Mass clonal propagation of improved conifers: field establishment of somatic embryo derived loblolly pine seedlings / Jerry Pullman, Paul Montello, Mike Cunningham ; Mass clonal propagation of improved conifers: functional anaylsis of pinus taeda zygotic embryo germination: the effect of partial drying and the acquisition of desiccation tolerance / Gary Peter ... [et al.] ; Mass clonal propagation of improved conifers: differential gene expression in the suspensor of zygotic embryos - update / John MacKay ... [et al.] ; Externally funded research in 1998-1999 supporting F010 / John Cairney ... [et al.] ; Gene expression studies with developing embryos: the effect of ABA treatment / Nanfei Xu ... [et al.] ; Early-stage-specific gene expression in loblolly pine zygotic and somatic embryos: cDNA cloning, sequencing and expression analysis / Vincent Ciavatta, Gerald Pullman and John Cairney ; Identification and cloning of cDNAs for novel female-, male- and vegetatively expressed genes / Lin Ge, Gerald Pullman, and John Cairney ; Fundamental biological mechanisms: improved stem growth rates and fiber properties: project F011 / Gary Peter ... [et al.] ; Fundamental biological mechanisms: improved fiber properties and rates of wood cell formation: cellulose biosynthesis / Gary Peter, Chris Ricker ; Externally funded reserach in 1998-1999 supporting F011 / Gary Peter ... [et al.] ; Towards genetic engineering of forest trees with anthraquinones: endogenous anthraquinones in pulpwood trees and the cloning of a key gene for anthraquinone biosynthesis / Huabin Meng ... [et al.] ; Environmental and genetic regulation of microfibril angle in southern pine: determination of the microfibril angle in the S2 layer of pinus taeda using differential interference contrast microscopy: validation of the method / Douglas Benton, Keith Bennett, Gary Peter ; Genetically modified lignin in pine: structure and properties: lignin reactivity in CAD-deficient trees during pulping and bleaching / Donald Dimmel ... [et al.] -- Slide material