MicroRNA-Mediated Calcineurin Signaling Activation Induces CCL2, CCL3, CCL5, IL8, and Chemotactic Activities in 4,4′-Methylene Diphenyl Diisocyanate Exposed Macrophages

Details

• Personal Author:
  Hettick JM ; Law, Brandon F. ; Lin C-C
• Description:
  Occupational exposure to 4,4'-methylene diphenyl diisocyanate (MDI), the most widely used monomeric diisocyanate, is one of the leading causes of occupational asthma (OA). Previously, we identified microRNA (miR)-206-3p/miR-381-3p-mediated PPP3CA/calcineurin signalling regulated iNOS transcription in macrophages and bronchoalveolar lavage cells (BALCs) after acute MDI exposure; however, whether PPP3CA/calcineurin signalling participates in regulation of other asthma-associated mediators secreted by macrophages/BALCs after MDI exposure is unknown. Several asthma-associated, macrophage-secreted mediator mRNAs from MDI exposed murine BALCs and MDI-glutathione (GSH) conjugate treated differentiated THP-1 macrophages were analysed using RT-qPCR. Endogenous IL1B, TNF, CCL2, CCL3, CCL5, and TGFB1 were upregulated in MDI or MDI-GSH conjugate exposed BALCs and macrophages, respectively. Calcineurin inhibitor tacrolimus (FK506) attenuated the MDI-GSH conjugate-mediated induction of CCL2, CCL3, CCL5, and CXCL8/IL8 but not others. Transfection of either miR-inhibitor-206-3p or miR-inhibitor-381-3p in macrophages induced chemokine CCL2, CCL3, CCL5, and CXCL8 transcription, whereas FK506 attenuated the miR-inhibitor-206-3p or miR-inhibitor-381-3p-mediated effects. Finally, MDI-GSH conjugate treated macrophages showed increased chemotactic ability to various immune cells, which may be attenuated by FK506. In conclusion, these results indicate that MDI exposure to macrophages/BALCs may recruit immune cells into the airway via induction of chemokines by miR-206-3p and miR-381-3p-mediated calcineurin signalling activation. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Isocyanates Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  4,4-Methylene Diphenyl Diisocyanate Author Keywords: 4,4'-methylene Diphenyl Diisocyanate (MDI) Bronchial Asthma Calcineurin Cell Signaling Diisocyanates Immune Cell Chemotaxis Macrophages MicroRNA (miR) Occupational Exposure Workers

  More +
• 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:
  51
• Issue:
  12
• NIOSHTIC Number:
  nn:20064226
• Citation:
  Xenobiotica 2021 Dec; 51(12):1436-1452
• Contact Point Address:
  Chen-Chung Lin, NIOSH/HELD/ACIB, 1000 Frederick Ln, MS L4020, Morgantown, WV 26505
• Email:
  mjy2@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  2022
• 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:f508cf14a45bc7e3132468bd6cc1cc0d8a9a3416ad3dfced311ac38d1a1121942a0e8e3f564fb886e0188da2b3a167e246c96b27f3057eba3d6741bff2edb1e2
• Download URL:
  https://stacks.cdc.gov/view/cdc/222729/cdc_222729_DS1.pdf
• File Type:
  [PDF - 4.18 MB ]