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Increased expression and immunoregulatory potential of microRNA 210 in a murine model of TDI sensitization.

Long-CM; Marshall-NB; Lukomska-E; Nayak-AP; Siegel-PD; Meade-BJ; Anderson-SE

Toxicologist 2015 Mar; 144(1):144-145

https://www.toxicology.org/pubs/docs/Tox/2015Tox.pdf

20045899

MicroRNAs are single-stranded RNAs that exhibit functional significance through the regulation of gene expression; however, their roles in chemical sensitization have not been elucidated. Toluene 2,4-diisocyanate (TDI) is a low molecular weight chemical sensitizer that causes occupational asthma. In order to investigate the functional role of miR-210 during TDI sensitization, BALBc mice were dermally exposed to TDI (0.5-4% v/v) and gene and protein expression were evaluated in the draining lymph nodes (dLN) and ears using RT-PCR and Western blot/ flow cytometry, respectively. Increased total serum IgE levels confirmed sensitization in these mice. Augmented miR-210 expression was observed in the dLN and ears following exposure to both irritating and non-irritating TDI concentrations. Increased expression of a potential miR-210 inducer, hif1alpha, was observed in the ears following TDI exposure. Alterations in expression of confirmed miR-210 transcription factor target foxp3 were observed in the dLN and ears and decreases in predicted targets' (foxp3, runx1, runx3, and smad4) mRNA expression were observed in the dLN of TDI-exposed mice. These transcription factors are involved in regulatory T cell (T-reg) expansion and function; therefore, miR-210 may play a functional role in TDI sensitization by potentially inhibiting T-reg differentiation and function. This hypothesis is supported by the T-reg population's kinetics and the presence of miR-210 in CD4 T cells during TDI sensitization. Because the roles of T-regs and miR-210 in chemical sensitization have not been elucidated these data contribute to the understanding of the immunologic mechanisms of chemical induced allergic disease and are critical for the development of preventative and therapeutic strategies.

Toxicology; Nanotechnology; Recombinant-DNA; Genes; Immune-system; Analytical-models; Toluenes; Isocyanates; Sensitization; Chemical-hypersensitivity; Laboratory-animals; Laboratory-testing; Exposure-assessment; Proteins; Lymph-nodes; Ears; Cell-alteration; Immunological-tests; Ribonucleic-acids; Cell-differentiation; Cell-function; Kinetics; Allergic-disorders

584-84-9

20150301

Abstract

2015

1

1096-6080

HELD

The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California

WV; CA