Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype
2021
Аутори:
Jonić, NatalijaChatzigiannis, Christos M.
Koprivica, Ivan
Savic, Anisia
Mićanović, Dragica
Saksida, Tamara
Pejnović, Nada
Tzakos, Andreas
Stojanović, Ivana D.
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
Метаподаци
Приказ свих података о документуАпстракт:
Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.
Кључне речи:
Biology of the immune system; immune regulation and therapy; macrophage; molecular immunologyУ:
- Abstracts of ECI 2021: 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. John Wiley and Sons; 2021. p. 207. (European Journal of Immunology; Vol. 51; No. S1).