Project description:The goal was to assess global gene expression changes in primary human bronchial epithelial cells exposed to environmental tobacco smoke (ETS) condensate. ETS-C was standardized by HPLC analysis and two timepoints of exposure in two different donor bronchial epithelial cell populations were assessed. These findings demonstrate that even short exposure (4.5 h) to ETS is sufficient to induce a stress response, as reflected by decreased antioxidant levels, induced HSP family members, and modulation of the family of glutathione metabolism enzymes in primary human lung cells. Upon longer exposures (48 h) with ETS-condensate, bronchial epithelial cells arrest at the G2/M phase of the cell cycle. Taken together, these data support a stress-induced state in primary human bronchial epithelial cells that culminates in cell cycle arrest. Keywords: time course, comparative, stress response
Project description:In this analysis we have used gene expression measurements form human bronchial epithelial cells following exposure to whole cigarette smoke.
Project description:This study aims to identify the proteomic targets of THC in the early postnatal hippocampus of developing mice. Therefore, early postnatal C57Bl/6 mice (P5) were exposed daily and for 30 days to plant extracted THC (either 1 mg/kg or 5 mg/kg) or vehicle solution (saline with 3% Tween® 80) for the control group. All animals stayed with their mothers until P25 and after the initial drug exposure time (until P35) animals were given a drug-free resting period. The animals were sacrificed, and their hippocampus was dissected and prepared for the following proteomic analysis at either P48 or after an extended resting period at P120. We found 31 proteins to be changed after THC exposure compared to vehicle at P48 and 186 proteins showing modifications at P120. Gene ontology classification of protein targets revealed a substantial amount of proteins involved in metabolic processes of neurons after THC exposure. The results highlight the vulnerability of the developing hippocampus towards THC exposure and identify the mitochondrial as well as other cell metabolic processes as potential drug targets.
Project description:Purpose: To understand the molecular mechanisms underlying Cd exposure-induced diseases. Methods: Immortalized human bronchial epithelial cells (BEAS-2B) were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM, Cellgro) supplemented with 1% Penicillin Streptomycin and 10% Fetal Bovine Serum (FBS, Atlanta Biologicals) at 37 degree C and 5 % CO2. For Cd exposure, 0, 2.5, 5 and 10 µM of CdCl2 was added to the media and the cells were cultured for 72h. Results: This study shows that cadmium exposure induces SNAIL1 expression via miR-30e downregulation and the cells undergo epithelial-mesenchymal transition.
Project description:We carry out a comparative proteomic analysis of human bronchial epithelial cells from patients clinically treated or not with inhaled budesonide and stimulated or not with the viral mimic Poly(I:C).We also wanted to investigate the potential anti-viral effects of imiquimod, a TLR7 agonist, on the bronchial epithelial cells proteome in vitro.
Project description:Cigarette smoke (CS) is a major risk factor in the development of chronic inflammatory lung diseases such as chronic obstructive pulmonary disease. To evaluate the biological impact of CS on lung tissue, three-dimensional (3D) organotypic bronchial tissue cultures can be used to replicate in vivo conditions. We developed an original 3D human bronchial epithelial co-culture model to assess the biological impact of repeated CS exposure on cell differentiation and on the inflammatory response. We found that CS can disrupt homeostatic capacity in a dose-dependent manner, and that the activation of the EGFR pathway, which is involved in the early-stage pathogenesis of airway diseases, was predicted from transcriptomic data. We believe that our model of bronchial tissues, used for repeated CS exposure, can provide valuable information on tissue-specific alterations in biological systems.
Project description:This SuperSeries is composed of the following subset Series:; GSE14383: Effects of chronic exposure of human bronchial epithelial cells to low doses of cigarette smoke condensate; GSE14385: Response of bronchial epithelial cells to low doses of cigarette smoke condensate and subsequent demethylation agent Experiment Overall Design: Refer to individual Series
Project description:Cannabis is commonly used in pregnancy for symptoms of nausea and pain, especially in the first trimester. Cannabis remains a federally illicit drug in the United States, but local legalization trends have resulted in increased availability and a decreased perception of harm. Unfortunately, limited scientifically rigorous information exists to inform decisions on use. Delta-9-tetrahydrocannabinol (THC, the main psychoactive component of cannabis) can cross the placenta and bind to cannabinoid receptor 1 (CB1) on the fetus. Because CB1 receptors are expressed in cardiomyocytes and endothelial cells, this suggests that THC exposure may impact fetal cardiovascular development. To understand this impact, our group used an established rhesus macaque model of chronic edible THC use during pregnancy. Animals were slowly titrated to a heavy THC dose (2.5mg/7kg/day) for 4 months preconception. Dams continued this daily THC dose throughout pregnancy with c-section delivery near term. Our model showed a decreased heart-to-body weight ratio from THC exposure. We examined the underlying changes in this selective fetal growth restriction of the cardiovascular system through tissue, protein, and gene expression analyses. H istological analysis of coronal sections of the heart and cross sections of the aorta showed no changes in collagen expression or maturity. Western blot analysis of collagen III expression showed no changes in left or right ventricle. Elastin expression was also unchanged in the aorta. To assess transcriptional changes, we performed bulk RNA-sequencing of vascular cells in the fetal aorta, umbilical vein, and umbilical artery, which revealed differentially expressed genes involved in metabolism and inflammation. These results suggest potential cardiovascular harm from in utero THC exposure by altering endothelial metabolism and inflammation.