Meta-analysis of primary target genes of peroxisome proliferator-activated receptors

A combined experimental and in silico approach identifies Peroxisome Proliferator Activated Receptor (PPAR) binding sites and six novel target genes in the human genome

Photocatalytic Decomposition of Formic Acid on Mo2C-Containing Catalyst

Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to filtered air and wood smoke. Samples were collected before (pre), at 24 h and 44 h after exposure, to air and wood smoke. Data are given as medians with interquartile range. (DOCX 62 kb

SOM analysis of established primary PPAR target genes, clusters III and IV

The genes were sorted by SOM analysis with respect to overall PPRE pattern similarity and their evolutionary conservation into cluster III and cluster IV. For more details, see the Figure 6 legend.<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of primary target genes of peroxisome proliferator-activated receptors"</p><p>http://genomebiology.com/2007/8/7/R147</p><p>Genome Biology 2007;8(7):R147-R147.</p><p>Published online 25 Jul 2007</p><p>PMCID:PMC2323243.</p><p></p

Extra-genomic functionality of the PPRE-containing promoter regions of PPAR target genes

Reporter gene assays were performed with extracts from HEK293 and HepG2 cells that were transiently transfected with reporter constructs containing genomic regions of eight human PPAR target genes (please note that the gene forms a cluster with the genes and ). These were co-transfected with empty expression vector (endogenous PPAR) or the indicated expression vectors for PPARα, PPARγ and PPARβ/δ. Cells were then treated for 16 h with solvent or PPAR subtype-specific ligands. Relative luciferase activity was determined and normalized to the activity of empty cloning vector control co-transfected with empty expression vector (dashed horizontal red line). The genomic regions were subdivided according to their location into close to TSS (a, d), upstream of TSS (b, e) and downstream of TSS (c, f); for further details see Figure 3 and Table 2. Columns represent the means of at least three experiments and bars indicate standard deviations. Two-tailed Student's -tests were performed to determine the significance of the ligand induction in reference to solvent controls (*< 0.05, **< 0.01, ***< 0.001).<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of primary target genes of peroxisome proliferator-activated receptors"</p><p>http://genomebiology.com/2007/8/7/R147</p><p>Genome Biology 2007;8(7):R147-R147.</p><p>Published online 25 Jul 2007</p><p>PMCID:PMC2323243.</p><p></p

Association of genomic regions of PPAR target genes with PPARs and their partner proteins

Chromatin was extracted from HEK293 cells that had been treated with solvent (DMSO) or for 120 minutes with 100 nM GW7647. The association of PPARα, RXRα and pPol II was monitored by ChIP assays with respective antibodies on genomic regions of the eight PPAR target genes that are close to the TSS, upstream of the TSS and downstream of the TSS; for location see Figure 3 and Table 2. Since the gene is not expressed in HEK293 cells, the data for its four genomic regions were obtained using chromatin derived from HepG2 cells. Real-time quantitative PCR was performed on chromatin templates and the fold change of the antibody-precipitated template in relation to an IgG-precipitated specificity control template was calculated. PPARα shows specific association with 15 of the 23 tested regions and the relative association with these regions is shown. Columns represent means of at least three experiments and bars indicate standard deviations. Two-tailed Student's -tests were performed to determine the significance of association in reference to IgG controls (*< 0.05, **< 0.01, ***< 0.001).<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of primary target genes of peroxisome proliferator-activated receptors"</p><p>http://genomebiology.com/2007/8/7/R147</p><p>Genome Biology 2007;8(7):R147-R147.</p><p>Published online 25 Jul 2007</p><p>PMCID:PMC2323243.</p><p></p

Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity

Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p &lt; 0.01, &lt; 0.05, &lt; 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (&lt; 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p &lt; 0.05, &lt; 0.05 and &lt; 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p &lt; 0.01, &lt; 0.05, &lt; 0.05 and &lt; 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure