MicroRNA-mediated calcineurin signaling activation induces CCL2, CCL3, CCL5, IL8, and chemotactic activities in 4,4′-methylene diphenyl diisocyanate exposed macrophages

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• Alternative Title:
  Xenobiotica
• Personal Author:
  Lin, Chen-Chung ; Law, Brandon F. ; Hettick, Justin M.
• 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 |-mediated PPP3CA/calcineurin signalling regulated | 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 |, |, |, |, |, and | 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 |, |, |, and | but not others. Transfection of either miR-inhibitor-206-3p or miR-inhibitor-381-3p in macrophages induced chemokine |, |, |, and | 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 | and |-mediated calcineurin signalling activation.
• Subjects:
  4,4′-methylene Diphenyl Diisocyanate (MDI) Animals Article Asthma, Occupational Calcineurin Chemokine CCL3 Immune Cell Chemotaxis Interleukin-8 Isocyanates Macrophages Mice MicroRNA (miR) MicroRNAs

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• Source:
  Xenobiotica. 51(12):1436-1452
• Pubmed ID:
  34775880
• Pubmed Central ID:
  PMC8915863
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  51
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:9b5caef9d31dbd5594568c83448ecd4433f8c8d69c3792be243c49e36d1a7d3f
• Download URL:
  https://stacks.cdc.gov/view/cdc/115439/cdc_115439_DS1.pdf
• File Type:
  [PDF - 1.05 MB ]