Project description:This study evaluated transcriptional effects of particles smaller than 100 nm of TiO2 and ZnO. Based on previous data in colon cancer cells (GSE14910), we evaluated HaCaT and Sk Mel-28 cells for transcriptional responses to 1 and 5 ug/cm2 ZnO, or 5 and 10 ug/cm2 TiO2. No particle controls were also included. Again, the most pronounced transcriptional response resulted from ZnO treatement with little responses to TiO2. We identified increased protein stress responses, decreased regulation of transcription, and responses to Zn ions. We did not observe the protein stress response and regulation of transcription with soluble Zn. Keywords: skin-derived cancer cells - response to ZnO nanoparticulate Two skin-derived cancer cell types (HaCaT and SK Mel-28) were treated with media containing the nanoparticulate, ZnCl2, or ZnO separated from the HaCaTs by a Transwell insert, and RNA was collected after 4 hrs. Generally, the RNA from 4 independent samples were combined for one microarray.
Project description:Analysis of lung CD11c+ antigen presenting cells (APCs) isolated from wildtype or Mir22-/- mice exposed to nanoparticulate carbon black (nCB) for one month. MiR-22 plays important roles in nCB induced experimental emphysema through regulating APC activation. Results provide insight into the biological role and target genes of miR-22. Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-kappaB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses.
Project description:This study evaluated transcriptional effects of particles smaller than 100 nm of carbon black, SiO2, Al2O3, TiO2, ZnO and Fe203. Since there is concern that inflammation may increase the uptake and/or toxicity of ultrafine particles, we evaluated the transcriptional responses without or with a TNFα pretreatment to mimic an inflammatory state. The most pronounced transcriptional response resulted from ZnO treatement, another response was to TNFα pre-treatment. We identified stress responses, responses to Zn ions, but did not observe a consistent proinflammatory response as evaluated by Gene Ontology of the genes that altered expression most as identified by significance analysis. Keywords: colon cancer cells - response to distinct nanoparticulate Two colon cancer cell types (RKO and CaCo-2) were pretreated with 100 ng/ml BSA or TNFα for 1 hr, the media was exchanged and with media containing the nanoparticulate, and RNA was collected after 4 hrs. Generally, the RNA from 4 independent samples were combined for one sample on the microarray, the exceptions were the TNFα treated controls where 6 independent samples were combined in 2 sets of 3 for the microarray labeling and hybridizations.
Project description:Concerns about the potential risks to human health due nanoparticulate pollution have been emerging. However, the risks to sensitive populations, such as pregnant individuals and their unborn children are poorly characterised. With increasing evidence of environmental particles passing the placenta, their potential adverse effects of on pregnancy and fetal development need to be assessed. Here, we investigated the impact of copper oxide (CuO) and polystyrene (PS) nanoparticle exposure on gene expression in ex vivo perfused human placental tissue.
Project description:Analysis of lung CD11c+ antigen presenting cells (APCs) isolated from wildtype or Mir22-/- mice exposed to nanoparticulate carbon black (nCB) for one month. MiR-22 plays important roles in nCB induced experimental emphysema through regulating APC activation. Results provide insight into the biological role and target genes of miR-22. Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-kappaB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses. Lung APCs were isolated from PBS (reference groups) or nCB exposed wildtype or Mir22-/- mice, total four groups. There were three replicates in each group.
Project description:This study evaluated transcriptional effects of particles smaller than 100 nm of carbon black, SiO2, Al2O3, TiO2, ZnO and Fe203. Since there is concern that inflammation may increase the uptake and/or toxicity of ultrafine particles, we evaluated the transcriptional responses without or with a TNFα pretreatment to mimic an inflammatory state. The most pronounced transcriptional response resulted from ZnO treatement, another response was to TNFα pre-treatment. We identified stress responses, responses to Zn ions, but did not observe a consistent proinflammatory response as evaluated by Gene Ontology of the genes that altered expression most as identified by significance analysis. Keywords: colon cancer cells - response to distinct nanoparticulate
Project description:This study evaluated transcriptional effects of particles smaller than 100 nm of TiO2 and ZnO. Based on previous data in colon cancer cells (GSE14910), we evaluated HaCaT and Sk Mel-28 cells for transcriptional responses to 1 and 5 ug/cm2 ZnO, or 5 and 10 ug/cm2 TiO2. No particle controls were also included. Again, the most pronounced transcriptional response resulted from ZnO treatement with little responses to TiO2. We identified increased protein stress responses, decreased regulation of transcription, and responses to Zn ions. We did not observe the protein stress response and regulation of transcription with soluble Zn. Keywords: skin-derived cancer cells - response to ZnO nanoparticulate
Project description:In this study, primary human monocyte-derived macrophages were exposed to plant-derived virus-like particles (VLPs) bearing influenza A hemagglutinin (HA) or soluble influenza HA, as control. Immunopurified MHC class I-associated peptides were analysed by nano-flow high pressure liquid chromatography coupled to high-resolution dopant-assisted electrospray ionisation mass spectrometry. A total of 109 host-derived MHC I peptides were identified in the VLP-treated samples, two of which were also detected in controls. The peptides unique to VLP treatment were, on average, ~13 amino acid residues long, more basic and hydrophilic, and were mainly processed via proteolysis by matrix metalloproteinases and cathepsins. The proteins associated with these peptides were primarily involved in cellular, metabolic and regulatory processes and activated several pathways including inflammation stimulation and attenuation, response to stimuli, innate and adaptive immunity, clathrin-mediated endocytosis, protein synthesis and endo-lysosomal degradation. This study is the first report to describe the response of a primary human antigen-presenting cell to nanoparticulate vs. soluble antigen exposure from an immunopeptidomics point of view.