Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/NW25-05-00121" target="_blank" >NW25-05-00121: Aryl uhlovodíkový receptor jako terapeutický cíl pro modulaci zánětlivé odpovědi ve střevě</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

TOXICOLOGY LETTERS

ISSN

—

e-ISSN

1879-3169

Svazek periodika

412

Číslo periodika v rámci svazku

OCT

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

11

Strana od-do

191-201

Kód UT WoS článku

001566195300001

EID výsledku v databázi Scopus

2-s2.0-105014994247