Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data of lung tissues from ICR mice treated with or without single-walled carbon nanotubes (SWCNTs)

ABSTRACT: The SWCNTs can induce airway hyper-responsiveness (AHR) and chronic obstructive pulmonary disease (COPD)-like changes in mice model. The SWCNTs can induce clusters of proteinases, chemokines/cytokines, and macrophage receptors triggered signaling, which might play critical roles in the SWCNTs-induced pathological changes, including chronic inflammation and tissues remodeling. We used microarrays to detail the global programme of gene expression underlying and identified distinct classes of up-regulated genes during this process. Lung tissues from adult ICR mice (6 weeks old) treated with or without single dose of 0.5 mg SWCNTs by intratrachael instillation were collected and homogenated under liquid nitrogen for RNA extraction and hybridization on Affymetrix microarrays. Since our data showed that the SWCNTs could induce significantly pulmonary granuloma and COPD-like lesion. Two time points of the samples have been collected for microarray analysis: day 1 after SWCNTs treatment as the acute phase responses; day 7 as the sub-chronic responses. We tried to compare the SWCNTs-regulated gene expression profiles with the PF68-treated (as the solvent control) to identify the possible mechanisms of SWCNTs-induced toxicity in lung.

ORGANISM(S): Mus musculus

SUBMITTER: Huei-Wen Chen

PROVIDER: E-GEOD-22856 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Single-walled carbon nanotubes (SWCNTs) are being explored and used for a wide range of applications in industrial and medical sectors, and the increasing exposure of SWCNTs necessitate the studies of their potential environmental and health effects. Considerable efforts have been made to improve the dispersion of SWCNTs by chemical modifications. The present study was designed to determine if the acid functionalization of SWCNTs enhanced the toxicity and more efforts were made to understand the molecular mechanisms. RAW264.7 cells were exposed to 0-100μg/mL of SWCNTs and AF-SWCNTs for 24 hours and cell proliferation, viability, and gene expression profiles were assessed and compared. Results showed that the magnitude of AF-SWCNT-induced cell proliferation inhibition was higher than that of SWCNTs. 10μg/mL of AF-SWCNTs was determined as non-toxic to cells by viability analysis. AF-SWCNTs could enter and aggregate in cell cytoplasm and nuclear areas. Microarray, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISA) demonstrated that AF-SWCNTs (1, 10, and 50μg/mL) altered gene and protein expression patterns. The most differentially expressed genes were related to pro-inflammatory cytokines and chemokines (such as CCL-3 and CCL-4), apoptosis (e.g., Caspase-1, -4, and Dffa), protective response (such as Hmox-1and GSTM3), and cell surface molecules such as ICAM-1, Itgb2, indicating a possible involvement of SWCNT in inflammation, anti-apoptotic and DNA fragmentation, carcinogenesis and biased T cell polarization. Furthermore, a substantial amount of down-regulated genes were found related to ribosomal assembly and mitochondrial respiration chain, implicating a possible mechanism of SWCNT-induced oxidative stress and gene expression inhibition. RAW264.7 gene expression after exposure to 1-50ug/ml AF-SWCNT-24 hours. 0ug/ml of AF-SWCNT was used as control sample. The data were obtained from three biological replicates.

Project description:Acute lung inflammation can alter the pulmonary function of susceptible individuals and exacerbate the pathogenesis of chronic inflammatory lung diseases including chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma. Exposure to lipopolysaccharide (LPS) or endotoxin, a constituent of outer cell membrane of gram negative bacteria, induces airway inflammation that is primarily characterized by increased polymorphonuclear neutrophils (PMNs) at early time points. Because LPS is present in variety of occupational and home environments and is an active constituent of cigarette smoke it is a risk factor for increasing prevalence and severity of non-occupational COPD, for adult onset of asthma and for wheezing in children. In airway epithelial cells, LPS stimulation increases mucin gene expression and mucous production. Hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality in chronic inflammatory respiratory lung diseases. In addition, acute bacterial infection contributes to the exacerbation of chronic airway diseases, specifically in advanced COPD and CF subjects, leading to increased healthcare burden and higher mortality. Bcl-2, a prosurvival protein that inhibits cell death plays a key role in normal cellular homeostasis and regulates the integrity of the mitochondrial and endoplasmic reticulum membranes. Gain- and loss-of-function studies showed that Bcl-2 expression sustains hyperplastic epithelial cells, and Bcl-2 expression is elevated in airway epithelial cells of subjects with cystic fibrosis and asthma. The present study investigated which inflammatory mediators induce mucous cell metaplasia and Bcl-2 expression following LPS exposure. Microarray analyses of mRNA from airway epithelial cells captured by laser microdissection from rat lungs snap-frozen at day 0 and 2 post LPS exposure were analyzed. Microarray analysis of mRNA from airway epithelial cells captured by laser microdissection from rat lungs snap-frozen at day 0 and day 2 post LPS exposure was performed to identify inflammatory mediators modulated by LPS exposure. Specific pathogen-free F344/NCrR male rats of 8–10 wk of age (from NCI, Frederick, MD) were exposed to LPS (1000 ug in 0.5 ML Saline) and rats were sacrificed on day 0 and day 2 of LPS exposure. Right lungs were snap-frozen in OCT and airway epithelial cells were captured by laser-dissection microsopy to extract RNA. Gene expression data from nonexposed rats (0d) was used a control.

Project description:As environmental pollutants and possible carcinogens, carbon nanotubes (CNTs) have recently been found to promote tumorigenesis and tumor metastasis after long-term pulmonary exposure. However, whether CNT-induced carcinogenesis can be inherited and last for generations remains unknown. Here, we establish a post-chronic single-walled carbon nanotubes (SWCNTs) exposed human bronchial epithelium BEAS-2B cell model to investigate SWCNTs-induced carcinogenesis. At a tolerated sublethal dose level, post-chronic SWCNTs exposure significantly increases the migration and colony formation abilities of BEAS-2B cells, leading to cell malignant transformation. Notably, the malignant transformation of BEAS-2B cells is irreversible within 60 days recovery period after SWCNTs exposure, and the malignant transformation activities of cells gradually increase during the recovery period. Mechanism analyses show that post-chronic exposure to SWCNTs causes substantial DNA methylation and transcriptome dysregulation of BEAS-2B cells. Subsequent enrichment and clinical database analyses reveal that differentially expressed/methylated genes of BEAS-2B cells are enriched in cancer-related biological pathways, and several of these genes are validated in lung cancer patients. As environmental pollutants and possible carcinogens, carbon nanotubes (CNTs) have recently been found to promote tumorigenesis and tumor metastasis after long-term pulmonary exposure. However, whether CNT-induced carcinogenesis can be inherited and last for generations remains unknown. Here, we establish a post-chronic single-walled carbon nanotubes (SWCNTs) exposed human bronchial epithelium BEAS-2B cell model to investigate SWCNTs-induced carcinogenesis. At a tolerated sublethal dose level, post-chronic SWCNTs exposure significantly increases the migration and colony formation abilities of BEAS-2B cells, leading to cell malignant transformation. Notably, the malignant transformation of BEAS-2B cells is irreversible within 60 days recovery period after SWCNTs exposure, and the malignant transformation activities of cells gradually increase during the recovery period. Mechanism analyses show that post-chronic exposure to SWCNTs causes substantial DNA methylation and transcriptome dysregulation of BEAS-2B cells. Subsequent enrichment and clinical database analyses reveal that differentially expressed/methylated genes of BEAS-2B cells are enriched in cancer-related biological pathways, and several of these genes are validated in lung cancer patients.

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Expression data of lung tissues from ICR mice treated with or without single-walled carbon nanotubes (SWCNTs)

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