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Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization.

Authors
Anderson-SE; Beezhold-K; Lukomska-E; Richardson-J; Long-C; Anderson-K; Franko-J; Meade-BJ; Beezhold-DH
Source
J Immunotoxicol 2014 Jul-Sep; 11(3):250-259
NIOSHTIC No.
20043479
Abstract
Allergic disease is an important occupational health concern, with work-related asthma and allergic contact dermatitis being the most frequently diagnosed occupational illnesses. Diisocyanates, particularly toluene 2,4-diisocyanate (TDI), have been the leading cause of occupational asthma for many years. Understanding the mechanisms behind allergic disease is critical for treatment and prevention. Recently, the study of post-transcriptional regulation by microRNAs (miRNA) has shed light on mechanisms of allergic disease. The present studies report the expression of miRNA during the sensitization phase of an allergic response to TDI in a murine model. Female BALB/c mice were dermally exposed to TDI (0.1-15% [v/v]) or vehicle. RNA was isolated from superficial parotid lymph nodes at timepoints between 1 h and 15 days post-exposure and then miRNA expression was analyzed using array and real-time quantitative PCR analysis. Consistent changes in miRNA expression were identified for miR-21, miR-22, miR-27b, miR-31, miR-126, miR-155, miR-210, and miR-301a. Following TDI exposure, peak expression was observed by Day 4 for the majority of miRNA evaluated with trends in expression correlated to exposure concentration. Confirmed and predicted targets were identified using Diana-microT, miRanda, miRwalk, and Targetscan algorithms. Evaluation of mRNA expression of cytokine and transcription factor targets suggests that miRNA may have a central role early in TDI sensitization. Understanding the role of these miRNA and their specific mechanism of action in sensitization to TDI may provide pertinent information for the identification of other chemical sensitizers while also contributing to the treatment and prevention of allergic disease.
Keywords
Bronchial-asthma; Toluenes; Isocyanates; Kinetics; Skin-sensitivity; Allergic-dermatitis; Allergies; Contact-allergies; Contact-dermatitis; Recombinant-DNA; Laboratory-animals; Laboratory-testing; Sensitization; Exposure-assessment; Exposure-levels; Cellular-reactions; Lymph-nodes; Bioassays; Author Keywords: Allergic disease; expression kinetics; miRNA; TDI chemical sensitization
Contact
Stacey E. Anderson, PhD, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Drive, Morgantown, WV 26505
CODEN
JIOMAP
CAS No.
584-84-9
Publication Date
20140701
Document Type
Journal Article
Email Address
sanderson4@cdc.gov
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
M122013
Issue of Publication
3
ISSN
1547-691X
NIOSH Division
HELD
Source Name
Journal of Immunotoxicology
State
WV; PA
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