Human Keratinocyte Response to 4,4′-Methylene Diphenyl Diisocyanate-Glutathione Conjugate Exposure

Details

• Personal Author:
  Hettick JM ; Law, Brandon F. ; Lin C-C
• Description:
  Workplace exposure to diisocyanates like 4,4'-methylene diphenyl diisocyanate can cause occupational asthma (MDI-OA), and the underlying biological pathways are still being researched. Although uncertainty remains, evidence supports the hypothesis that dermal exposure to MDI plays an important role in the development of MDI-OA. Gene expression, proteomics, and informatics tools were utilised to characterise changes in expression of RNA and protein in cultured human HEKa keratinocyte cells following exposure to conjugates of MDI with glutathione (MDI-GSH). RT-qPCR analysis using a panel of 39 candidate primers demonstrated 9 candidate genes upregulated and 30 unchanged. HPLC-MS/MS analysis of HEKa cell lysate identified 18 540 proteins across all samples 60 proteins demonstrate statistically significant differential expression in exposed cells, some of which suggest activation of immune and inflammatory pathways. The results support the hypothesis that dermal exposures have the potential to play an important role in the development of MDI-OA. Furthermore, proteomic and gene expression data suggest multiple immune (adaptive and innate) and inflammatory pathways may be involved in the development of MDI-OA. [Description provided by NIOSH]
• Subjects:
  Asthma, Occupational Immune System Isocyanates Occupational Health Safety Skin
• Keywords:
  4,4-Methylene Diphenyl Diisocyanate Author Keywords: 4'-methylene Diphenyl Diisocyanate Dermal Exposures Gene Expression Human Keratinocytes Immune Reaction Label-free Quantitative Proteomics MDI OA Occupational Asthma
• ISSN:
  0049-8254
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  54
• Issue:
  9
• NIOSHTIC Number:
  nn:20070123
• Citation:
  Xenobiotica 2024 Sep; 54(9):749-758
• Contact Point Address:
  Brandon F. Law, PhD., NIOSH/HELD/ACIB, 1095 Willowdale Rd., MS L4020, Morgantown, WV 26505
• Email:
  bhl7@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  2024
• Peer Reviewed:
  True
• Source Full Name:
  Xenobiotica
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fce1e14e0b7f52a34a3c2b1e38d00aa914ea1c208da8e8db0e3d596349da35f2bd769753bd612a4ce4f2b7f3f1c1da2363e398cbccce835bf6f5aa4b6607217d
• Download URL:
  https://stacks.cdc.gov/view/cdc/208408/cdc_208408_DS1.pdf
• File Type:
  [PDF - 1.82 MB ]