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Alterations in DNA Methylation Correlate with a Th17 Driven Immune Response in the Lung Due to Multi-Walled Carbon Nanotube Exposure

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Multi-walled carbon nanotubes (MWCNT) are one of the most widely produced and used engineered nanomaterials. Exposure to MWCNT has been associated with pathological changes in the lungs of mice, raising concerns about potential human health effects. Although there is intense interest in describing the effects of MWCNT on airway inflammation, the underlying molecular mechanisms remain unclear. Accumulating evidence from studies on DNA methylation supports the idea that epigenetic mechanisms following environmental exposures leads to inflammation and disease. To elucidate the underlying epigenetic mechanisms leading to MWCNT induced inflammation, we performed pyrosequencing assay to assess the level of promoter methylation in acute inflammatory related genes (Il-6, Il-1b, Cxcl1, Il-5 and Il-4). There were pathological responses to MWCNT at both 24 h and 7 days following MWCNT exposure, indicating a Th17 type inflammatory response. This included substantial increases in IL-6 and CXCL1 release at 24 h and increased tissue pathology at 7 days, including airway remodeling. There was a significant decrease in the levels of DNA methylation at the Il-6 and Cxcl1 promoter in 24 h MWCNT exposed mice compared with controls (p < 0.05). The obtained results show that alterations in gene specific methylation of inflammatory related genes correlate with initial immune response and the development of Th17 driven inflammation and tissue pathology. Given the data, we suggest that DNA methylation is a potential mechanism in the progression of murine lung inflammation and injury caused by MWCNT.
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Keywords: Airway Remodeling; Inflammation; Multi-Walled Carbon Nanotubes; Promoter Methylation; Th17

Document Type: Research Article

Affiliations: Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Missoula, MT 59812, USA

Publication date: August 1, 2016

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  • Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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