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In vitro assessment of mechanistic events induced by structurally related chemical rubber sensitizers

Lindberg, Tim LU ; Forreryd, Andy LU ; Bergendorff, Ola LU ; Lindstedt, Malin LU and Zeller, Kathrin S. LU (2019) In Toxicology in Vitro 60. p.144-153
Abstract

Allergic contact dermatitis (ACD) is one of the most common forms of immunotoxicity, and increased understanding of how chemicals trigger these adverse reactions is needed in order to treat or design testing strategies to identify and subsequently avoid exposure to such substances. In this study, we investigated the cellular response induced by rubber chemicals in a dendritic cell (DC) model, focusing on the structurally similar chemicals diethylthiocarbamylbenzothiazole sulfide and dimethylthiocarbamylbenzothiazole sulfide, with regard to regulation of microRNA, and messenger RNA expression. Only a few miRNAs were found to be commonly regulated by both rubber chemicals, among them miR1973, while the overall miRNA expression profiles... (More)

Allergic contact dermatitis (ACD) is one of the most common forms of immunotoxicity, and increased understanding of how chemicals trigger these adverse reactions is needed in order to treat or design testing strategies to identify and subsequently avoid exposure to such substances. In this study, we investigated the cellular response induced by rubber chemicals in a dendritic cell (DC) model, focusing on the structurally similar chemicals diethylthiocarbamylbenzothiazole sulfide and dimethylthiocarbamylbenzothiazole sulfide, with regard to regulation of microRNA, and messenger RNA expression. Only a few miRNAs were found to be commonly regulated by both rubber chemicals, among them miR1973, while the overall miRNA expression profiles were diverse. Similarly, out of approximately 500 differentially regulated transcripts for each chemical, about 60% overlapped, while remaining were unique. The pathways predicted to be enriched in the cell model by stimulation with the rubber chemicals were linked to immunological events, relevant in the context of ACD. These results suggest that small structural differences can trigger specific activation of the immune system in response to chemicals. The here presented mechanistic data can be valuable in explaining the immunotoxicological events in DC activation after exposure to skin sensitizing chemicals, and can contribute to understanding, preventing and treating ACD.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microRNA, Potency, Rubber sensitizers, Skin sensitization, Transcriptomics
in
Toxicology in Vitro
volume
60
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85066024340
ISSN
0887-2333
DOI
10.1016/j.tiv.2019.05.006
language
English
LU publication?
yes
id
f7f941f1-39a8-4db5-a255-04da7c46bb79
date added to LUP
2019-06-11 08:31:19
date last changed
2019-06-25 03:55:21
@article{f7f941f1-39a8-4db5-a255-04da7c46bb79,
  abstract     = {<p>Allergic contact dermatitis (ACD) is one of the most common forms of immunotoxicity, and increased understanding of how chemicals trigger these adverse reactions is needed in order to treat or design testing strategies to identify and subsequently avoid exposure to such substances. In this study, we investigated the cellular response induced by rubber chemicals in a dendritic cell (DC) model, focusing on the structurally similar chemicals diethylthiocarbamylbenzothiazole sulfide and dimethylthiocarbamylbenzothiazole sulfide, with regard to regulation of microRNA, and messenger RNA expression. Only a few miRNAs were found to be commonly regulated by both rubber chemicals, among them miR1973, while the overall miRNA expression profiles were diverse. Similarly, out of approximately 500 differentially regulated transcripts for each chemical, about 60% overlapped, while remaining were unique. The pathways predicted to be enriched in the cell model by stimulation with the rubber chemicals were linked to immunological events, relevant in the context of ACD. These results suggest that small structural differences can trigger specific activation of the immune system in response to chemicals. The here presented mechanistic data can be valuable in explaining the immunotoxicological events in DC activation after exposure to skin sensitizing chemicals, and can contribute to understanding, preventing and treating ACD.</p>},
  author       = {Lindberg, Tim and Forreryd, Andy and Bergendorff, Ola and Lindstedt, Malin and Zeller, Kathrin S.},
  issn         = {0887-2333},
  keyword      = {microRNA,Potency,Rubber sensitizers,Skin sensitization,Transcriptomics},
  language     = {eng},
  pages        = {144--153},
  publisher    = {Elsevier},
  series       = {Toxicology in Vitro},
  title        = {In vitro assessment of mechanistic events induced by structurally related chemical rubber sensitizers},
  url          = {http://dx.doi.org/10.1016/j.tiv.2019.05.006},
  volume       = {60},
  year         = {2019},
}