The Diacetyl-Exposed Human Airway Epithelial Secretome: New Insights into Flavoring-Induced Airways Disease

Details

• Personal Author:
  Brass DM ; Brinkley CD ; Foster MW ; Gwinn WM ; Kelly FL ; Morgan DL ; Moseley MA ; Nagler AE ; Palmer SM ; Valente AMl
• Description:
  Bronchiolitis obliterans (BO) is an increasingly important lung disease characterized by fibroproliferative airway lesions and decrements in lung function. Occupational exposure to the artificial food flavoring ingredient diacetyl, commonly used to impart a buttery flavor to microwave popcorn, has been associated with BO development. In the occupational setting, diacetyl vapor is first encountered by the airway epithelium. To better understand the effects of diacetyl vapor on the airway epithelium, we used an unbiased proteomic approach to characterize both the apical and basolateral secretomes of air-liquid interface cultures of primary human airway epithelial cells from four unique donors after exposure to an occupationally relevant concentration (approximately 1,100 ppm) of diacetyl vapor or phosphate-buffered saline as a control on alternating days. Basolateral and apical supernatants collected 48 h after the third exposure were analyzed using one-dimensional liquid chromatography tandem mass spectrometry. Paired t tests adjusted for multiple comparisons were used to assess differential expression between diacetyl and phosphate-buffered saline exposure. Of the significantly differentially expressed proteins identified, 61 were unique to the apical secretome, 81 were unique to the basolateral secretome, and 11 were present in both. Pathway enrichment analysis using publicly available databases revealed that proteins associated with matrix remodeling, including degradation, assembly, and new matrix organization, were overrepresented in the data sets. Similarly, protein modifiers of epidermal growth factor receptor signaling were significantly altered. The ordered changes in protein expression suggest that the airway epithelial response to diacetyl may contribute to BO pathogenesis. [Description provided by NIOSH]
• Subjects:
  Chromatography Diacetyl Environmental Exposure Flavoring Agents Lung Lung Diseases Men Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Solvents Women

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• Keywords:
  Author Keywords: 2,3-butanedione Bronchiolitis Bronchiolitis Obliterans Diseases Exposure Levels Flavorings Food Food Additives Humans Lung Disease Lung Lesions Occupational Lung Disease Pathogenesis Proteomics Pulmonary Disorders Pulmonary Effects Pulmonary System Pulmonary System Disorders Respiratory Diseases Respiratory System Disorders Risk Factors Vapors

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• ISSN:
  1044-1549
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  56
• Issue:
  6
• NIOSHTIC Number:
  nn:20050305
• Citation:
  Am J Respir Cell Mol Biol 2017 Jun; 56(6):784-795
• Contact Point Address:
  David M. Brass, M.D., Duke University Medical Center, 2100 MSRB II DUMC 103002, Durham, NC 27710
• Email:
  david.brass@duke.edu
• CAS Registry Number:
  Butanedione (CAS RN 431-03-8)
• Federal Fiscal Year:
  2017
• Performing Organization:
  Duke University
• Peer Reviewed:
  True
• Start Date:
  20140901
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• End Date:
  20160831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5352cdcf65b8322bc0e256861eab91b5a72e8caaf571f51c66afcfdef2e1b276fc727a99e0a7fd7ab3c3e9400123d4697074f75f9f576145369fe4034004ff05
• Download URL:
  https://stacks.cdc.gov/view/cdc/210713/cdc_210713_DS1.pdf
• File Type:
  [PDF - 970.76 KB ]