|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ИНХС РАН |
||
Bedaquiline enhances receptor phagocytosis and decreases IL1b production in human pro-inflammatory macrophagesтезисы доклада Тезисы
- Авторы: Pavlova Ekaterina, Erokhina Maria
- Сборник: European Respiratory Journal
- Том: 58
- Тезисы
- Год издания: 2021
- Издательство: European Respiratory Society
- Местоположение издательства: Switzerland
- Первая страница: PA2480
- DOI: 10.1183/13993003.congress-2021.pa2480
- Аннотация: Bedaquiline (BDQ) is one of the modern antibiotics for MDR-tuberculosis (TB) therapy. Its immunomodulatory properties have not yet been studied. The aim of our work was to reveal BDQ effects on the functional activity of pro-inflammatory (M1) human macrophages. BDQ effects (5 μg/ml) were assessed at different stages of M1-macrophage differentiation (MD) which was induced in THP-1 monocytic cell line by 100 nM PMA. We used RT-PCR to analyze genes expression of cytokines and key phagocytic receptors, multiplex analysis to determine the level of cytokines and flow cytometry to assess phagocytosis of mannan and IgG-latex beads. THP-1 M1 macrophages are characterized by the high levels of: (i) expression of TNF, IL1b and IL6 and Fc receptor (CD64) genes; (ii) production of TNF, IL1b and IL6 cytokines; (iii) phagocytosis activity of IgG latex beads. The phagocytosis receptor genes DC-SIGN (CD209) and MRC1 (CD206) are expressed at a low level. In the early stages of MD, BDQ significantly increased in the CD64 and CD209 gene expression and does not affect the CD206 expression. Also, under the BDQ, the cells phagocytic activity was elevated. Also, BDQ reduced IL1b gene expression by 2 times, and the level of the secreted cytokine - more than 6 times. No effects on the gene expression and secretion of TNF, IL6 and IL10 were found. The BDQ effects were less pronounced in the late stages of THP-1 MD, but the receptor phagocytosis was significantly increased. Thus, we revealed therapeutically valuable immunomodulatory BDQ effects on M1 macrophages: increase in receptor phagocytosis is important in the fight against pathogens and decrease of IL1b production to restrain TB inflammation.
- Добавил в систему: Павлова Екатерина Николаевна