Project description:Air pollution is an environmental risk factor linked to multiple human diseases including cardiovascular diseases (CVDs). While particulate matter (PM) emitted by diesel exhaust damages multiple organ systems, heart disease is one of the most severe pathologies affected by PM. However, the in vivo effects of diesel exhaust particles (DEP) on the heart and the molecular mechanisms of DEP-induced heart dysfunction have not been investigated. In the current study, we attempted to identify the proteomic signatures of heart fibrosis caused by diesel exhaust particles (DEP) in CVDs-prone apolipoprotein E knockout (ApoE-/-) mice model using tandem mass tag (TMT)-based quantitative proteomic analysis. DEP exposure induced mild heart fibrosis in ApoE-/- mice compared with severe heart fibrosis in ApoE-/- mice that were treated with CVDs-inducing peptide, angiotensin II. TMT-based quantitative proteomic analysis of heart tissues between PBS- and DEP-treated ApoE-/- mice revealed significant upregulation of proteins associated with platelet activation and TGFβ-dependent pathways. Our data suggest that DEP exposure could induce heart fibrosis, potentially via platelet-related pathways and TGFβ induction, causing cardiac fibrosis and dysfunction.
Project description:The mechanisms by which diesel exhaust particles act as an adjuvant are unknown. We hypothesized that these would be mediated through monocyte interactions with DEP. We sought to identify pathways with a role in inflammation or other signaling mechanisms that might demonstrate the mechanism of response to DEP. Cultured human monocytes from healthy donors were cultured in the presence or absence of diesel exhaust particles. RNA was extracted following culture to determine changes in gene expression pathways.
Project description:Epidemiological studies have linked exposure to ambient particulate matter (PM) with increased asthmatic symptoms. Diesel exhaust particles (DEP) are a predominant source of vehicle derived ambient PM, and experimental studies have demonstrated that they may have adjuvant potential when given with an antigen. We previously compared 3 DEP samples: N-DEP, A-DEP, and C-DEP in a murine ovalbumin (OVA) mucosal sensitization model and reported the adjuvant activity to be: C-DEP ? A-DEP > N-DEP. The present study analyzed gene expression changes from the lungs of these mice. Transcription profiling demonstrated that all the DEP samples altered cytokine and toll-like receptor pathways regardless of type, with or without antigen sensitization. Further analysis of DEP exposure with OVA showed that all DEP treatments altered networks involved in immune and inflammatory responses. The A- and C-DEP/OVA treatments induced differential expression of apoptosis pathways in association with stronger adjuvant responses, while expression of cell cycle control and DNA damage pathways were also altered in the C-DEP/OVA treatment. This comprehensive approach using gene expression analysis to examine changes at a pathway level provides detailed information on events occurring in the lung after DEP exposure, and confirms that the most bioactive sample induced many more individual genes and changes in immuno-regulatory and homeostatic pathways. Female BALB/C mice (8-10 weeks old) were randomly divided into 8 treatment groups containing 3 mice each and exposed to saline, 20 ug ovalbumin, 150 ug diesel exhaust particles (either C-DEP, A-DEP, or N-DEP), or diesel exhaust particles + ovalbumin by intranasal instillation on Days 0 and 13 and necropsied 18 hrs latter.
Project description:The potential of diesel exhaust particles (DEP) to transform human bronchial epithelial cells (HBEC3) was investigated and a stably transformed cell line (T2-HBEC3) was established. Short-term DEP exposure experiments adds information of immunomodulatory effect markers and differences in susceptibility between normal and sensitized bronhial epithelial cells of the human lung.
Project description:The mechanisms by which diesel exhaust particles act as an adjuvant are unknown. We hypothesized that these would be mediated through monocyte interactions with DEP. We sought to identify pathways with a role in inflammation or other signaling mechanisms that might demonstrate the mechanism of response to DEP.
Project description:We evaluated the profile of lncRNA and mRNA expression in control and 50μg/ml DEP treated HBE cells using the Arraystar Human LncRNA Array v3.0 array,7th generation. Our findings implicates that dysregulation of mitochondria invovled mRNAs may play important role in cytotoxicity of DEP. Examination of lncRNA and mRNA expression in control or DEP-treated HBE cells
Project description:Recently air pollution has become serious environmental issues effect. Contaminated air by pollutants, such as emission of diesel fuel, enter the human body through airway tract and can cause inflammatory diseases in respiratory system. The relation between air pollutant and development of respiratory diseases have well-studied, but the processes of disease outbreak were not fully studied yet. We investigated global gene expression induced by diesel exhaust particle (DEP), one of air pollutants in primary human nasal epithelial cell (PHNEC) with the purpose of identifying potential biomarkers. Furthermore, we analyzed signaling pathway among differentially expressed genes (DEGs) for elucidating signaling networks of process developing airway diseases. Consequentially, we suggested several key biomarkers that include not only the expression changes but also the meaning of relation between genes. This findings might be used for early diagnosis and prevention of upper respiratory disease, especially rhinitis.
Project description:We evaluated the profile of lncRNA and mRNA expression in control and 50μg/ml DEP treated HBE cells using the Arraystar Human LncRNA Array v3.0 array,7th generation. Our findings implicates that dysregulation of mitochondria invovled mRNAs may play important role in cytotoxicity of DEP.
Project description:The pulmonary response to inhalation exposure to diesel exhaust particles (DEP) was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol containing DEP at concentrations of 200 or 1000 mg/m3, 6 hours/day for 4 days. The control and DEP-exposed rats were euthanized at post-exposure time intervals of 1, 7, or 27 days and pulmonary inflammatory, cytotoxic and oxidant responses were determined. Analysis of bronchoalveolar lavage parameters of toxicity such as lactate dehydrogenase activity, oxidant generation, and inflammation did not reveal any significant pulmonary toxicity in the DEP-exposed rats. The lung gene expression profiles did not change significantly in the DEP exposed rats compared with the controls. The data obtained from the present study demonstrated that DEP inhalation exposure under the conditions employed in the present study did not result in any significant lung toxicity in the rats.