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Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl.

Publication ,  Journal Article
Foster, MW; Gwinn, WM; Kelly, FL; Brass, DM; Valente, AM; Moseley, MA; Thompson, JW; Morgan, DL; Palmer, SM
Published in: J Proteome Res
February 3, 2017

Occupational exposures to the diketone flavoring agent, diacetyl, have been associated with bronchiolitis obliterans, a rare condition of airway fibrosis. Model studies in rodents have suggested that the airway epithelium is a major site of diacetyl toxicity, but the effects of diacetyl exposure upon the human airway epithelium are poorly characterized. Here we performed quantitative LC-MS/MS-based proteomics to study the effects of repeated diacetyl vapor exposures on 3D organotypic cultures of human primary tracheobronchial epithelial cells. Using a label-free approach, we quantified approximately 3400 proteins and 5700 phosphopeptides in cell lysates across four independent donors. Altered expression of proteins and phosphopeptides were suggestive of loss of cilia and increased squamous differentiation in diacetyl-exposed cells. These phenomena were confirmed by immunofluorescence staining of culture cross sections. Hyperphosphorylation and cross-linking of basal cell keratins were also observed in diacetyl-treated cells, and we used parallel reaction monitoring to confidently localize and quantify previously uncharacterized sites of phosphorylation in keratin 6. Collectively, these data identify numerous molecular changes in the epithelium that may be important to the pathogenesis of flavoring-induced bronchiolitis obliterans. More generally, this study highlights the utility of quantitative proteomics for the study of in vitro models of airway injury and disease.

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Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

February 3, 2017

Volume

16

Issue

2

Start / End Page

538 / 549

Location

United States

Related Subject Headings

  • Young Adult
  • Volatilization
  • Respiratory Mucosa
  • Proteome
  • Primary Cell Culture
  • Phosphorylation
  • Molecular Sequence Annotation
  • Middle Aged
  • Male
  • Keratin-6
 

Citation

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Foster, M. W., Gwinn, W. M., Kelly, F. L., Brass, D. M., Valente, A. M., Moseley, M. A., … Palmer, S. M. (2017). Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl. J Proteome Res, 16(2), 538–549. https://doi.org/10.1021/acs.jproteome.6b00672
Foster, Matthew W., William M. Gwinn, Francine L. Kelly, David M. Brass, Ashlee M. Valente, M Arthur Moseley, J Will Thompson, Daniel L. Morgan, and Scott M. Palmer. “Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl.J Proteome Res 16, no. 2 (February 3, 2017): 538–49. https://doi.org/10.1021/acs.jproteome.6b00672.
Foster MW, Gwinn WM, Kelly FL, Brass DM, Valente AM, Moseley MA, et al. Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl. J Proteome Res. 2017 Feb 3;16(2):538–49.
Foster, Matthew W., et al. “Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl.J Proteome Res, vol. 16, no. 2, Feb. 2017, pp. 538–49. Pubmed, doi:10.1021/acs.jproteome.6b00672.
Foster MW, Gwinn WM, Kelly FL, Brass DM, Valente AM, Moseley MA, Thompson JW, Morgan DL, Palmer SM. Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl. J Proteome Res. 2017 Feb 3;16(2):538–549.
Journal cover image

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

February 3, 2017

Volume

16

Issue

2

Start / End Page

538 / 549

Location

United States

Related Subject Headings

  • Young Adult
  • Volatilization
  • Respiratory Mucosa
  • Proteome
  • Primary Cell Culture
  • Phosphorylation
  • Molecular Sequence Annotation
  • Middle Aged
  • Male
  • Keratin-6