Ligand-regulated expression of TNF receptors 1 and 2 determines receptor-mediated functional responses

Alina Alshevskaya, Olga Koneva, Irina Belomestnova, Julia Lopatnikova, Irina Evsegneeva, Julia Zhukova, Fedor Kireev, Aleksander Karaulov, Sergey Sennikov

    Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

    Аннотация

    Introduction: Modulating specific biological effects through the changes in cytokine receptors' expression level remains poorly understood. This study aimed to investigate the influence of the dose-dependent effect of TNF on the balance between proapoptotic and proliferation response depending on the parameters of TNFR1/2 expression density. Methods: Tumor cell lines (HEp-2, K-562, MCF-7, ZR-75/1, MOLT-4, IM-9, and Raji) were characterized for TNFR1/2 co-expression using flow cytometry and were studied to reveal the dose-dependent effect of rhTNF on cell cycle and apoptosis parameters. The associations among the studied parameters were estimated by correlation and regression analysis. Results: It was found for ZR-75/1 cells (the cell line characterized by high expression of both types) that a dose-dependent increase in expression of both types of TNF-α receptors on cells reduces the proliferative activity of cells. For MOLT-4 cells (which are characterized by lower expression), an increase in proliferative response of cells was positively associated with the percentage of both TNFR1+ and TNFR2+ cells. However, opposite effects on the cells were shown for the K-562 and MCF-7 lines having a similar expression profile. A similarity (a large percentage of double-positive cells) was revealed for the lines having similar effects (K-562 and ZR-75/1). Conclusions: High expression of TNF receptor type 1 is not always associated with predominant activation of proapoptotic pathways. However, in the case of simultaneous high expression of both types of receptors, the proportion of double-positive cells is crucial for the activation of either the proapoptotic or proliferation pathways.

    Язык оригиналаанглийский
    Страницы (с-по)1077-1088
    Число страниц12
    ЖурналInternational Archives of Allergy and Immunology
    Том182
    Номер выпуска11
    Ранняя дата в режиме онлайн1 июн 2021
    DOI
    СостояниеОпубликовано - 1 ноя 2021

    Предметные области OECD FOS+WOS

    • 3.02 КЛИНИЧЕСКАЯ МЕДИЦИНА
    • 3.02.AQ АЛЛЕРГИЯ
    • 3.01 ФУНДАМЕНТАЛЬНАЯ МЕДИЦИНА
    • 3.01.NI ИММУНОЛОГИЯ

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