Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor
2021
Аутори:
Jonić, NatalijaChatzigiannis, Christos M.
Koprivica, Ivan
Savić, Anisia
Mićanović, Dragica
Saksida, Tamara
Pejnović, Nada
Tzakos, Andreas
Stojanović, Ivana D.
Остала ауторства
Spasojević, IvanТип документа:
Конференцијски прилог (Објављена верзија)
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© 2021 by the Faculty of Chemistry and the Serbian Biochemical Society
Метаподаци
Приказ свих података о документуАпстракт:
A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Spasojević I, editor. Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. Belgrade: Faculty of Chemistry: Serbian Biochemical Society; 2021. p. 69-70.