Вопросы вирусологии. 2020; 65: 284-293
Интерферон-регулирующая активность противовирусного лекарственного средства целагрип и его влияние на экспрессию генов врожденного иммунитета и образование активных форм кислорода у больных фолликулярной лимфомой
https://doi.org/10.36233/0507-4088-2020-65-5-5Аннотация
Введение. Лекарственные средства из группы индукторов интерферона (IFN) «включают» синтез интерферонов 1-го типа (IFN-I) и индуцируют экспрессию IFN-стимулированных генов (ISG), которые регулируют реакции врожденного иммунитета и защищают хозяина от инфекционных агентов и опухолевой патологии.
Цель исследования – определить роль лекарственного средства (ЛС) целагрип (ЦА) в активации генов врожденного иммунитета и влиянии на продукцию активных форм кислорода у больных фолликулярной лимфомой (ФЛ). Задачи: изучить интенсивность продукции активных форм кислорода (АФК) и уровень экспрессии генов IFN-α2, IFN-λ1, ISG15, BCL2, P53(ТР53) и USP18 в ответ на обработку ЦА клеток крови больных ФЛ.
Материал и методы. В исследовании участвовали первичные онкологические пациенты с диагнозом ФЛ и здоровые добровольцы, у которых выполнен кинетический анализ динамики продукции АФК клетками крови и определена экспрессия группы генов методом полимеразной цепной реакции в реальном времени в ответ на обработку ЦА.
Результаты и обсуждение. Выявлено статистически достоверное снижение продукции АФК клетками крови больных ФЛ и здоровых добровольцев в присутствии ЦА (P < 0,05). Кратность стимуляции генов ISG15, P53(ТР53) и USP18 в группе больных ФЛ значительно превышала таковую в группе здоровых добровольцев. При обработке ЦА клеток крови становится возможным разделить больных ФЛ на группы с положительным и отрицательным ответом в соответствии с уровнем экспрессии гена USP18.
Выводы. ЦА снижает продукцию АФК и одновременно стимулирует активность генов врожденного иммунитета ISG15, P53(ТР53) и USP18 в клетках крови больных ФЛ.
Список литературы
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33. Kitareewan S., Pitha-Rowe I., Sekula D., Lowrey C.H., Nemeth M.J., Golub T.R. et al. UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia. Proc. Natl. Acad. Sci. USA. 2002; 99(6): 3806–11. https://doi.org/10.1073/pnas.052011299
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Problems of Virology. 2020; 65: 284-293
Interferon-regulating activity of the celagrip antiviral drug and its influence on formation of reactive oxygen species and expression of innate immunity genes in the follicular lymphoma patients
https://doi.org/10.36233/0507-4088-2020-65-5-5Abstract
Introduction. Medicines from the group of interferon inducers (IFNs) “swith on” the synthesis of type 1 interferons (IFN-I) and induce the expression of IFN-stimulated genes (ISGs) that regulate innate immunity reactions and protect the host from infectious agents and the tumour pathology.
The purpose of the study was to determine the role of the drug celagrip (CA) in the activation of innate immunity genes and the effect on the production of reactive oxygen species (ROS) in patients with follicular lymphoma (FL).
Objectives: to study the intensity of ROS production and the level of expression of the IFN-α2, IFN-λ1, ISG15, BCL2, P53(TP53) and USP18 genes in response to the treatment of blood cells of patients with FL with the preparation of CA.
Material and methods. The study involved primary cancer patients diagnosed with follicular lymphoma (FL) and healthy volunteers. A kinetic analysis of the dynamics of production of reactive oxygen species (ROS) was performed in whose blood cells, and the expression of the group of genes was determined by real-time PCR in response to CA processing.
Results and discussion. ROS production by blood cells of patients with FL and volunteers in the presence of CA significantly decreased (P < 0.05). The level of gene expression of ISG15, P53(TR53) and USP 18 in the group of patients with FL was significantly higher than that in the group of volunteers. When treating blood cells with CA, it becomes possible to divide patients with FL into groups with a positive and negative response in accordance with the level of expression of the USP18 gene. We divided FL patients into groups with a positive and negative response in accordance with the level of USP18 gene expression after treatment of blood cells with CA.
Conclusions. The CA drug reduces the production of ROS and simultaneously stimulates the activity of the innate immunity genes ISG15, P53(TP53) and USP18 in the blood cells of patients with FL.
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30. Andersen J.B., Aaboe M., Borden E.C., Goloubeva O.G., Hassel B.A., Orntoft T.F. Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer. Br. J. Cancer. 2006; 94(10): 1465–71. https://doi.org/10.1038/sj.bjc.6603099
31. Desai S.D., Haas A.L., Wood L.M., Tsai Y.C., Pestka S., Rubin E.H., et al. Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res. 2006; 66(2): 921–8. https://doi.org/10.1158/0008-5472.can-05-1123
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