Project description:In this study gene expression of monocyte-derived macrophages (MDM) from chronic obstructive pulmonary disease (COPD) patients and healthy subjects was investigated. MDM were treated with LPS, a combination of fine TiO2 and ultrafine Printex90 particles, or remained untreated. Experiment Overall Design: MDM of 13 COPD patients and 13 healthy subjects were incubated for four hours with LPS (10ng/ml), a combination of fine TiO2 and ultrafine Printex90 (32ug/ml each) or remained untreated. Cells were harvested, counted, and total RNA was isolated (phenol-chloroform extraction) for each subject individually. Total RNA of the 13 individuals from each group (COPD, healthy) and incubation (untreated, LPS, particles) were pooled and hybridized on a seperate array.
Project description:In this study gene expression of monocyte-derived macrophages (MDM) from chronic obstructive pulmonary disease (COPD) patients and healthy subjects was investigated. MDM were treated with LPS, a combination of fine TiO2 and ultrafine Printex90 particles, or remained untreated. Keywords: disease state analysis
Project description:The purpose of this study was to characterize global gene expression in human airway epithelial cells and identify cellular pathways associated with coarse, fine and ultrafine particulate matter (PM) exposures. Ambient PM was collected in 3 different size fractions from Chapel Hill air, particles were extracted from foam or filter matrices and lyophilized. Human primary airway epithelial cells were exposed to particles at 250μg/ml or vehicle control for 6h in culture. Following exposure, RNA was isolated and hybridized to human HG U133A affymetrix chips. Experiment Overall Design: Human primary epithelial cells were exposed to coarse, fine, ultrafine PM or vehicle control in culture for 6h. Three biological replicates for each treatment (coarse, fine, ultrafine, control) were conducted at (250ug/ml). 12 Affymetrix chips (HG U133A) were used.
Project description:Peripheral blood samples were collected before (0 hour) and at 24 hours after exposure from healthy subjects who participated in previous controlled exposures to ultrafine carbon particles (UFP, 50 microg/m3) or filtered air (FA)(n = 3 each). The exposure time was 2 hours. RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. We used microarray to explore significantly altered genes after ultrafine carbon particle exposure.
Project description:Peripheral blood samples were collected before (0 hour) and at 24 hours after exposure from healthy subjects who participated in previous controlled exposures to ultrafine carbon particles (UFP, 50 microg/m3) or filtered air (FA)(n = 3 each). The exposure time was 2 hours. RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. We used microarray to explore significantly altered genes after ultrafine carbon particle exposure. Each subject was exposed to filtered air or ultrafine carbon particles. Two peripheral blood samples (pre- and post-exposure) were taken. Mononuclear cells were isolated for gene expression analysis.
Project description:Gene expression profiling of the human keratinocytes cell line (HaCaT) exposure to ultrafine, fine, and submicron TiO2 particles were employed to gain insights into the molecular events.
Project description:The purpose of this study was to characterize global gene expression in human airway epithelial cells and identify cellular pathways associated with coarse, fine and ultrafine particulate matter (PM) exposures. Ambient PM was collected in 3 different size fractions from Chapel Hill air, particles were extracted from foam or filter matrices and lyophilized. Human primary airway epithelial cells were exposed to particles at 250μg/ml or vehicle control for 6h in culture. Following exposure, RNA was isolated and hybridized to human HG U133A affymetrix chips. Keywords: particle treatment
Project description:Rationale: COPD (Chronic Obstructive Pulmonary Disease) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar (AM) and peripheral monocyte-derived (MDM) macrophages, we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AM and MDM from COPD and healthy donors underwent functional, metabolic and transcriptional profiling. Results: We observe that AM and MDM from COPD donors display a critical depletion in glycolytic and mitochondrial respiration derived energy reserves and an over reliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH generating enzyme, malic enzyme 1, a known target of the anti-oxidant transcription factor NRF2. Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance and a recovery of macrophage function. Conclusion: In COPD an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.
Project description:Study the training exercise effects in chronic obstructive pulmonary disease (COPD) patients and aged-matched healthy individuals. Skeletal muscle biopsies from 9 stable COPD patients with normal fat free mass index (FFMI, 21Kg/m2) (COPDN), 6 COPD patients with low FFMI (16Kg/m2) (COPL), and 12 healthy sedentary subjects (FFMI 21Kg/m2) before and after 8 weeks of a supervised endurance exercise program were analyzed.
Project description:Genome wide DNA methylation profiling of Chronic Obstructive Pulmonary Disease (COPD) patients and healthy subjects. The Illumina Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across in peripheral blood mononuclear cell samples. Samples included 6 normal subjects and 12 COPD patients among which 3 of them have 2nd samples from follow-up examination.
