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: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:C57BL/6 mice were exposed to vehicle or 0.162 mg carbon black nanoparticles by intratracheal installation and were sacrificed 1, 3 and 28 days post-exposure. Gene expression was investigated in two sets of mice treated according to the identical exposure protocol. MicroRNAs were investigated in the second set of mice.
Project description:We reportWe used bulk RNA sequencing technology to profile gene expression in human pluripotent stem cell-derived type 2 alveolar cell-like cells. By obtaining over 15,000 genes, we compared the derived alveolar cell-like cells to H9 embryonic stem cells. We found significant down-regulation of several pluripotency genes whereas activation of lung or alveolus marker genes, and thus suggested successful induction. We treated the derived cells with nano carbon black and sequenced the samples in order to obtain differentially expressed genes due to the treatment. From KEGG analysis, we concluded that expression of most genes inferring lung or alveolus identities were not affected by the treatment. However, pathways such as chemical carcinogenesis and xenobiotic metabolism were significantly promoted. Finally, since organoid culture is trendy, we compared monolayer-derived alveolar cell-like cells to organoid-based derived ones. Results showed overall similarity in gene expression yet organoid culture yielded morphologically and structurally better cells. This study uses bulk RNA sequencing to confirm the alveolar induction from human pluripotent stem cells and provides insights for nano carbon black toxicities in alveolar cells.
Project description:C57BL/6 mice were exposed to vehicle or 0.162 mg carbon black nanoparticles by intratracheal installation and were sacrificed 1, 3 and 28 days post-exposure. Gene expression was investigated in two sets of mice treated according to the identical exposure protocol. MicroRNAs were investigated in the second set of mice.
Project description:C57BL/6 mice were exposed to vehicle or 0.162 mg carbon black nanoparticles by intratracheal installation and were sacrificed 1, 3 and 28 days post-exposure. Gene expression was investigated in two sets of mice treated according to the identical exposure protocol. MicroRNAs were investigated in the second set of mice.
Project description:Recent in vivo studies reported that inhaled carbon nanotube distribute in the alveolar region resulting in an acute inflammation, progressive fibrotic response and particle accumulation at the bronchoalveolar junction with low clearance. With similar biopersistence and shape as asbestos, a known lung carcinogen, growing concern has arisen for elevated risk of carbon nanotube-induced lung carcinogenesis; however few studies have evaluated long-term human health risks associated with chronic pulmonary carbon nanotube exposures compared to asbestos. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single walled carbon nanotube, multi-walled carbon nanotube and crocidolite asbestos to human small airway epithelial cells to assess their neoplastic transformation potential. Subchronic single-, multi-walled carbon nanotube and asbestos exposures caused human lung cell neoplastic transformation exhibited by increased proliferation, anchorage-independent growth, invasion and angiogenesis. Whole genome profiling and protein expression analyses showed that carbon nanotube-induced transformation mechanism(s) was largely different from asbestos-related inflammatory signaling, suggesting specific carbon nanotube-induced carcinogenic potential. This study provides novel carbon nanotube and asbestos toxicogenomic information for risk assessment and an in vitro model to evaluate transformation potential of carbon nanotubes and other nanoparticles. Whole genome expression profiling was conducted on human immortalized small airway epithelial cells (SAEC-hTERT) following 6 month in vitro chronic exposure to six separate treatments to assess differences in carbon nanotube (CNT) vs. asbestos potential tumorigenesis signaling. Dispersed single wall CNT (D-SWCNT), multi-wall CNT (D-MWCNT), ultrafine carbon black (D-UFCB), crocidolite asbestos (ASB) and saline (SAL) exposed cells were compared to SurvantaM-BM-. dispersant (DISP) passage control cells. Each treatment possessed 3 biological cDNA replicates. One technical replicate was performed per biological sample.
Project description:To identify differentially expressed genes and key biological pathways that define toxicity following nanomaterial exposure, we performed microarray analyses on NR8383 macrophages exposed for 4 h to 0.9 cm²/cm² of carbon black (Printex 90). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement N°. 686098
Project description:We investigated hepatic mRNA profiles of female mice exposed to 0.162 mg Printex 90 carbon black nanoparticles by single intra-tracheal instillation. We examined responses to this dose 1, 3 and 28 days after exposure, alongside respective controls. We show that genes part of the 3-hydroxy-3-methyl-glutaryl-CoA reductase pathway to be up-regulated by exposure to Printex 90.
Project description:This SuperSeries is composed of the following subset Series: GSE36170: Pulmonary miRNA expression in C57BL/6 Bom Tac mice (dams) intratracheally instilled with Printex 90 carbon black nanoparticles GSE36171: Pulmonary miRNA expression in C57BL/6 non-pregnant female mice intratracheally instilled with Printex 90 carbon black nanoparticles Refer to individual Series
