4,4′-Methylene Diphenyl Diisocyanate Exposure Induces Expression of Alternatively Activated Macrophage-Associated Markers and Chemokines Partially Through Krüppel-Like Factor 4 Mediated Signaling in Macrophages

Details

• Personal Author:
  Hettick JM ; Law, Brandon F. ; Lin C-C
• Description:
  Occupational exposure to the most widely used monomeric diisocyanate (dNCO), 4,4'-methylene diphenyl diisocyanate (MDI), may lead to the development of occupational asthma (OA). Alveolar macrophages with alternatively activated (M2) phenotype have been implicated in allergic airway responses and the pathogenesis of asthma. Recent in vivo studies demonstrate that M2 macrophage-associated markers and chemokines are induced by MDI-exposure, however, the underlying molecular mechanism(s) by which this proceeds is unclear. Following MDI exposure (in vivo and in vitro) M2 macrophage-associated transcription factors (TFs), markers, and chemokines were determined by RT-qPCR, western blots, and ELISA. Expression of M2 macrophage-associated TFs and markers including Klf4/KLF4, Cd206/CD206, Tgm2/TGM2, Ccl17/CCL17, Ccl22/CCL22, and CCL24 were induced by MDI/MDI-GSH exposure in bronchoalveolar lavage cells (BALCs)/THP-1 macrophages. The expression of CD206, TGM2, CCL17, CCL22, and CCL24 are upregulated by 3.83-, 7.69-, 6.22-, 6.08-, and 1.90-fold in KLF4-overexpressed macrophages, respectively. Endogenous CD206 and TGM2 were downregulated by 1.65-5.17-fold, and 1.15-1.78-fold, whereas CCL17, CCL22, and CCL24 remain unchanged in KLF4-knockdown macrophages. Finally, MDI-glutathione (GSH) conjugate-treated macrophages show increased chemotactic ability to T-cells and eosinophils, which may be attenuated by KLF4 knockdown. Our data suggest that MDI exposure may induce M2 macrophage-associated markers partially through induction of KLF4. [Description provided by NIOSH]
• Subjects:
  Asthma, Occupational Blood Isocyanates Lung Macrophages Occupational Health Respiratory System Safety
• Keywords:
  4,4'-methylene Diphenyl Diisocyanate 4,4-Methylene Diphenyl Diisocyanate Author Keywords: Occupational Asthma Diisocyanates DNCOs Gene Expression KLF4 Krüppel-like Factor 4 Lung Cells M2 Macrophage Polarisation MDI Molecular Signaling OA Occupational Asthma

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• 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:
  53
• Issue:
  12
• NIOSHTIC Number:
  nn:20068890
• Citation:
  Xenobiotica 2023 Dec; 53(12):653-669
• Contact Point Address:
  Chen-Chung Lin, Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA
• Email:
  mjy2@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Xenobiotica
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:efe7e8c36a0154dd2fc62b240401dd0126d51373cd5a3cf18986edb9c9650fb266cd7a114fb91a41d7d9694339adc56e2da55e6042672fece641e4e8b7458937
• Download URL:
  https://stacks.cdc.gov/view/cdc/207455/cdc_207455_DS1.pdf
• File Type:
  [PDF - 3.09 MB ]