Proteomics of Flavorings-Induced Airway Disease
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2017/01/16
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Series: Grant Final Reports
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Description:The overall goal of our research is to improve the diagnosis and treatment of bronchiolitis obliterans (BO) that occurs in the workplace as a result of exposure to artificial flavors. Workers in the food manufacturing industry are at significant risk for occupational airway disease due to exposure to commonly used artificial flavorings. In particular, diacetyl (DA) used in butter flavoring has been linked to the development of bronchiolitis obliterans (BO), an irreversible airway fibrosis. As a result, NIOSH NORA objectives include strategic goals focused on work-related airway diseases, specifically targeting studies of "diacetyl and other potentially harmful artificial flavorings" to improve workplace risk assessment (Goal 5.2.2) and define mechanisms of toxicity (Goal 5.1.3). This proposal directly addressed the NIOSH objectives for the Manufacturing Sector and Respiratory Disease Cross-sector. Under the R21 two year funding mechanism progress was completed towards the primary goal of this project to identify novel biomarkers of early lung injury after exposure to the artificial flavors such as DA. We treated human bronchial epithelial cells (NHBE) cells with DA in occupationally relevant concentrations. We then demonstrated differential expression of proteins (i.e. the secretome) basally, apically, and intracellularly from cultured NHBE in vitro at an air-liquid interface in response to DA using state-of-the-art proteomic analysis technology. The study specific aims as performed were to 1) Quantify changes in the basolateral and apical secretomes of NHBE cells grown under physiological conditions after exposure to DA and determine the cellular pathways activated by flavoring exposures and 2) Quantify changes in the intracellular proteome and phosphoproteome of NHBE cells grown under physiological conditions after exposure to DA and determine the cellular pathways activated by flavoring exposures. Our unbiased discovery based approach has identified potential novel biomarkers of flavoring toxicity that could improve early recognition of airway toxicity in the workplace and will provide new insights into disease mechanisms if validated through further in vitro and in vivo studies. [Description provided by NIOSH]
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Pages in Document:1-43
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NIOSHTIC Number:nn:20052067
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NTIS Accession Number:PB2019-101098
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Citation:Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R21-OH-010490, 2017 Jan; :1-43
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Federal Fiscal Year:2017
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Performing Organization:Duke University
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Peer Reviewed:False
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Start Date:20140901
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Source Full Name:National Institute for Occupational Safety and Health
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End Date:20160831
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Main Document Checksum:urn:sha-512:ed1f0a60e9dee0a182a8c44ffe9d89ef7811ca0bfd62f0f81d2f164751b3413148051faa772614afbbac3d5a705011a62b65664579f697f521d06953855cf22f
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