Downregulation of Circulating miRs-206-3p and -381-3p May Serve As Putative Serum Biomarkers for Detection of 4,4’-Methylene Diphenyl Diisocyanate Exposure
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Chen-Chung Lin, Ph.D., Brandon F Law, M.S., Paul D. Siegel, Ph.D., Justin M. Hettick, Ph.D.

Occupational exposure to the most widely used diisocyanate, 4,4’-methylene diphenyl diisocyanate (MDI), is a cause of occupational asthma (OA). Early recognition of MDI sensitization and control of MDI exposure is essential for the prevention of MDI-OA, however, there are no accepted immunological tests for identification of MDI-OA. Circulating microRNAs (miRs) have been proposed as biomarkers for asthma, cancers, and other diseases. We hypothesize that circulating miRs can be identified and used as biomarkers of MDI-OA.


Female BALB/c mice were either dermally exposed to 1% MDI in acetone for 3 consecutive days or nose-only exposed to air or 4580 ± 1497 µg/m3 MDI aerosol for 60 minutes. Blood was collected at 24 hours after last exposure of dermally exposed mice or at 4 hours or 24 hours post exposure of nose-only exposed mice. Exiqon miR qPCR array was used to profile circulating miRs from dermally exposed mice. Candidate miRs were verified in serum from either dermal or nose-only exposed mice by stem-loop TaqMan miR qPCR assays on an ABI7500 realtime PCR instrument.


Serum mmu-miR-206-3p and mmu-miR-381-3p were downregulated 1.59-fold and 6.31-fold in dermal MDI-exposed mice compared to acetone vehicle exposed mice. In the MDI aerosol exposure murine model, serum mmu-miR-206-3p was downregulated 10.26-fold at 4 hours post-exposure and 3.36-fold 24 hours post-exposure compared to control. Serum mmu-miR-381-3p was downregulated 8.06-fold at 4 hours post-MDI aerosol exposure and 3.71-fold at 24hours post-MDI aerosol exposure compared to control.


Downregulation of serum miRs-206-3p and -381-3p may serve as biomarkers of MDI sensitization and OA.