Harding, A.L., Murdoch, C. orcid.org/0000-0001-9724-122X, Danby, S. et al. (6 more authors) (2021) Determination of chemical irritation potential using a defined gene signature set on tissue-engineered human skin equivalents. JID Innovations, 1 (2). 100011. ISSN 2667-0267
Abstract
There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made based on the evaluation of clinical presentations including burning, prickling, erythema and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents (HSE) based on immortalised skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full thickness HSE or human ex vivo skin and gene signatures determined for known irritants and non-irritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2 and MMP-3) that could distinguish potential irritants from non-irritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Funding Information: | Funder Grant number HIGHER EDUCATION INNOVATION FUND nan |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Mar 2021 13:30 |
Last Modified: | 27 Apr 2021 16:12 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.xjidi.2021.100011 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:172596 |