Conventional and toxicogenomic assessment of the acute pulmonary damage induced by the instillation of Cardiff PM10 into the rat lung

Wise, Hannah; Balharry, Dominique; Reynolds, Lucy; Sexton, Keith John; Richards, Roy J.

doi:10.1016/j.scitotenv.2005.08.056

Cited by 19 publications

(12 citation statements)

References 13 publications

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“…Limited information exists concerning the toxicogenomic effects of PM on lung tissue, a viable strategy for the identification of potential molecular biomarkers that may reflect the pulmonary toxicity of PM exposure (Andre et al 2006; Koike et al 2004; Kooter et al 2005; Leikauf et al 2001; Roberts et al 2004; Wise et al 2006). Because asthmalike parameters peaked 3–7 days after PM treatment (Walters et al 2001), we chose day 4 after PM exposure as the time point to assess the impact of PM on lung tissue genome regulation, a time point of maximal synergy with OVA sensitization.…”

Section: Discussionmentioning

confidence: 99%

Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness

Wang

Moreno‐Vinasco

Huang

et al. 2008

Environ Health Perspect

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BackgroundAsthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma prevalence and exacerbations.ObjectiveWe investigated pathophysiologic responses to Baltimore, Maryland, ambient PM (median diameter, 1.78 μm) in a murine model of asthma and attempted to identify PM-specific genomic/molecular signatures.MethodsWe exposed ovalbumin (OVA)-sensitized A/J mice intratracheally to PM (20 mg/kg), and assayed both AHR and bronchoalveolar lavage (BAL) on days 1, 4, and 7 after PM exposure. Lung gene expression profiling was analyzed in OVA- and PM-challenged mice.ResultsConsistent with this murine model of asthma, we observed significant increases in airway responsiveness in OVA-treated mice, with PM exposure inducing significant changes in AHR in both naive mice and OVA-induced asthmatic mice. PM evoked eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of type 1 T helper (TH1) cytokines [interferon-γ, interleukin-6 (IL-6), tumor necrosis factor-α] and TH2 cytokines (IL-4, IL-5, eotaxin) into murine airways. Furthermore, PM consistently induced expression of genes involved in innate immune responses, chemotaxis, and complement system pathways.ConclusionThis study is consistent with emerging epidemiologic evidence and indicates that PM exposure evokes proinflammatory and allergic molecular signatures that may directly contribute to the asthma susceptibility in naive subjects and increased severity in affected asthmatics.

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Section: Discussionmentioning

confidence: 99%

Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness

Wang

Moreno‐Vinasco

Huang

et al. 2008

Environ Health Perspect

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“…With the powerful “-omics” tools (i.e., genome-wide molecular profiling technologies such as microarrays and sequencing) now readily available, multiple aspects of cellular response to PM exposure have been studied: gene transcription (transcriptome) [6, 32–38], DNA methylation (methylome) [39–45], and protein-level expression (proteome) [46–54]. As PM exposure takes place with every inhalation, a life-time exposure to PM occurs for the majority of the general population.…”

Section: Pm-mediated Cardiopulmonary Toxicogenomicsmentioning

confidence: 99%

Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective

Wang¹,

Garcia²,

Zhang³

2012

CPPM

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Particulate matter (PM) air pollution exerts significant adverse health effects in global populations, particularly in developing countries with extensive air pollution. Understanding of the mechanisms of PM-induced health effects including the risk for cardiovascular diseases remains limited. In addition to the direct cellular physiological responses such as mitochondrial dysfunction and oxidative stress, PM mediates remarkable dysregulation of gene expression, especially in cardiovascular tissues. The PM-mediated gene dysregulation is likely to be a complex mechanism affected by various genetic and non-genetic factors. Notably, PM is known to alter epigenetic markers (e.g., DNA methylation and histone modifications), which may contribute to air pollution-mediated health consequences including the risk for cardiovascular diseases. Notably, epigenetic changes induced by ambient PM exposure have emerged to play a critical role in gene regulation. Though the underlying mechanism(s) are not completely clear, the available evidence suggests that the modulated activities of DNA methyltransferase (DNMT), histone acetylase (HAT) and histone deacetylase (HDAC) may contribute to the epigenetic changes induced by PM or PM-related chemicals. By employing genome-wide epigenomic and systems biology approaches, PM toxicogenomics could conceivably progress greatly with the potential identification of individual epigenetic loci associated with dysregulated gene expression after PM exposure, as well the interactions between epigenetic pathways and PM. Furthermore, novel therapeutic targets based on epigenetic markers could be identified through future epigenomic studies on PM-mediated cardiopulmonary toxicities. These considerations collectively inform the future population health applications of genomics in developing countries while benefiting global personalized medicine at the same time.

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“…I.T. administration of PM also leads to up-regulation of infl ammatory genes (Ayres et al 2008 ;Wang et al 2008 ;Wise et al 2006 ). Suwa et al found that I.T.…”

Section: Role Of the Lungs In Mediating Systemic Effectsmentioning

confidence: 99%

Air Pollution, Lipids and Atherosclerosis

Araujo

Rosenfeld

2015

Molecular and Integrative Toxicology

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Conventional and toxicogenomic assessment of the acute pulmonary damage induced by the instillation of Cardiff PM10 into the rat lung

Cited by 19 publications

References 13 publications

Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness

Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness

Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective

Air Pollution, Lipids and Atherosclerosis

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