An immunologic role of microRNA 210 in a murine model of dermal toluene-2,4-diisocyanate sensitization.
Long CM; Marshall NB; Siegel PD; Meade BJ; Lukomska E; Anderson KL; Beezhold D; Anderson SE
Toxicologist 2014 Mar; 138(1):34
Diisocyanates, such as toluene 2, 4-diisocyanate (TDI) are the principal cause of occupational asthma induced by low molecular weight chemicals. Recently, the study of immune regulation by microRNAs has revealed the importance of these regulatory molecules in allergic disease. Our laboratory has shown that miRNA 210 (miR-210) expression increases in the draining lymph nodes (DLN) following dermal exposure to TDI in a murine model, however, the role of miR-210 in allergic disease is unknown. These studies were conducted to elucidate the functional role of miR-210 during sensitization to TDI. Female BALB/c mice were dermally exposed to TDI (4%) or vehicle. RNA was isolated from specific cellular subsets (T-cells and B-cells) at four days post exposure and analyzed for miR-210 expression using real-time quantitative polymerase chain reaction analysis. A statistically significant increase in miR-210 expression occurred in the DLN CD4+ cell population of TDI-exposed mice. Confirmed (foxp3) and predicted (runx1t1, runx3, smad4, and stat6) miR-210 transcription factor targets were identified using computational algorithms. Augmentations in foxp3 protein expression and decreases in runx1 and foxp3 mRNA occurred concurrently with expression of miR-210 following dermal TDI exposure. Understanding the immunologic mechanisms of allergic disease is critical for the development of preventative and therapeutic strategies and these studies suggest a functional role for miR-210 in the regulatory T cell pathway and ultimately in the pathogenesis of TDI sensitization.
Toxicology; Chemical-properties; Bronchial-asthma; Molecular-structure; Allergic-reactions; Allergies; Diseases; Laboratory-testing; Lymph-nodes; Exposure-levels; Laboratory-animals; Animals
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona