Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F25%3A73633116" target="_blank" >RIV/61989592:15310/25:73633116 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0378427425015760" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378427425015760</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.toxlet.2025.09.001" target="_blank" >10.1016/j.toxlet.2025.09.001</a>
Alternative languages
Result language
angličtina
Original language name
Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line
Original language description
Disruption of the epidermal barrier contributes to skin disorders such as atopic dermatitis and psoriasis. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays a key role in skin homeostasis and immune regulation. While traditionally associated with toxicity, AhR has emerged as a promising therapeutic target, particularly via tryptophan-derived indoles. To support AhR research in a dermatological context, we developed AhaRaCaT, a stable luciferase-based reporter cell line derived from human keratinocytes (HaCaT), enabling the assessment of AhR transcriptional activity in a skin-relevant model. We characterized the inducibility of AhaRaCaT in response to model AhR ligands (TCDD, BaP, FICZ) in dose- and time-dependent assays. Antagonist profiling with MNF, CH223191, GNF, carvone, and jasmone yielded IC50 values over 4- and 24-hour exposures. A panel of indoles previously studied in other models was evaluated for AhR activation, revealing a robust luciferase response at 4 h that declined at 24 h, consistent with trends observed in other cell types. Selected indoles also induced CYP1A1 mRNA expression and reversed cytokine-induced downregulation of filaggrin in HaCaT cells, highlighting their potential in mitigating inflammation-associated skin barrier defects. In summary, the AhaRaCaT cell line offers a sensitive and physiologically relevant tool for studying AhR signaling in skin, with broad applications in toxicology, dermatological research, and the development of AhR-targeted therapies for inflammatory skin diseases.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
<a href="/en/project/NW25-05-00121" target="_blank" >NW25-05-00121: Modulating the inflammatory response in the gut by targeting the aryl hydrocarbon receptor as a therapeutic goal</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
TOXICOLOGY LETTERS
ISSN
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e-ISSN
1879-3169
Volume of the periodical
412
Issue of the periodical within the volume
OCT
Country of publishing house
IE - IRELAND
Number of pages
11
Pages from-to
191-201
UT code for WoS article
001566195300001
EID of the result in the Scopus database
2-s2.0-105014994247