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Вопросы вирусологии. 2019; 64: 165-172

Цитокин-регулирующая активность противовирусного препарата ЦелАгрип в перевиваемых В-клеточных линиях лимфомы Беркитта

Наровлянский А. Н., Мезенцева М. В., Суетина И. А., Руссу Л. И., Иванова А. М., Полосков В. В., Изместьева А. В., Оспельникова Т. П., Сарымсаков А. А., Ершов Ф. И.

https://doi.org/10.36233/0507-4088-2019-64-4-165-172

Аннотация

Введение. Цитокины, активируемые в ответ на иммуносупрессивные вирусные инфекции, могут прямо или косвенно влиять на неопластическую трансформацию В-клеток. В настоящем исследовании изучали новую субстанцию, разработанную для получения противовирусного лекарственного средства ЦелАгрип (CelAgripus, ЦА), которая проявляет интерферон- (ИФН) и цитокин-индуцирующую активность и, по-видимому, может быть использована в качестве активатора противовирусного иммунитета.

Цель исследования - оценить цитокин-регулирующее действие ЦА в линиях клеток лимфомы Беркитта (ЛБ), латентно инфицированных вирусом Эпштейна-Барр (ВЭБ).

Авторам предстояло изучить ЦА-индуцированную экспрессию генов цитокинов - интерлейкинов (ИЛ) -1р, -2, -4, -6, -8, -10, -12, -17, -18; ИФН-а, -Y, -в, -А1, -Л2, -Л3; фактора некроза опухоли а (ФНОа) в нормальных и трансформированных ВЭБ клетках ЛБ.

Материал и методы. Использовали линии клеток фибробластов эмбриона человека (ФЭЧ), Namalva, Daudi, Raji и Р3НR-1, на которых изучали препараты ЦА, госсипол-уксусной кислоты (ГУК), натрий-карбоксиметилцеллюлозы (Na-КМЦ) с помощью методов ОТ-ПЦР и оценки цитотоксичности.

Результаты. Выявлено действие ЦА на экспрессию генов ИФН-Л, ИЛ-1р, ИЛ-6, ИЛ-8 и ИЛ-10. Направленность цитокинового ответа зависела от вида клеток и дозы препарата.

Обсуждение. При обработке ЦА клеток ЛБ наблюдались активация генной экспрессии ИФН-Л, ИЛ-1Р, -6, -8 и супрессия активности гена ИЛ-10. При действии субстанций Na-КМЦ и ГУК, используемых для синтеза ЦА, выявлено, в основном, подавление экспрессии генов ИФН-р, ИЛ-1Р, ИЛ-10, ИЛ-18 и ФНОа.

Заключение. Субстанция ЦА оказывает новые эффекты по активации экспрессии ряда ключевых цитокиновых генов в перевиваемых линиях клеток ЛБ. Направленность цитокинового ответа зависит от вида клеток и дозы препарата.

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Problems of Virology. 2019; 64: 165-172

Cytokine-regulating activity of anti-virus preparation CelAgripus in Burkitt's lym-phoma stable B-cell lines

Narovlyansky A. N., Mezentseva M. V., Suetina I. A., Russu L. I., Ivanova A. M., Poloskov V. V., Izmest'eva A. V., Ospelnikova T. P., Sarymsakov A. A., Ershov F. I.

https://doi.org/10.36233/0507-4088-2019-64-4-165-172

Abstract

Introduction. Cytokines activated in response to immunosuppressive viral infections can directly or indirectly affect the neoplastic transformation of B cells. In this study, we studied a new substance designed to produce the antiviral drug CelAgrip (CA, CelAgripus), which exhibits interferon (IFN) and cytokine-inducing activity and, apparently, can be used as an activator of antiviral immunity.

Purpose - is to evaluate the cytokine-regulating effect of CA in Burkitt's lymphoma (LB) cell lines latently infected with the Epstein-Barr virus (EBV).

Objectives: to study the CA-induced expression of the cytokine genes IL-ip, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, IFN-a, IFN -Y, IFN-p, IFN-A1, IFN-A2, IFN-A3, TNF-a in normal and EBV transformed LB cells.

Material and methods. Cell line: the human embryo fibroblasts (HEF), Namalva, Daudi, Raji, P3HR-1. Preparations: CA, gossypol-acetic acid (GAA), sodium carboxymethyl cellulose (Na-CMC). Methods: RT-PCR and methods for assessing cytotoxicity (MTT and Scepter 2.0 Merck cell counter).

Results. The effect of the CA preparation on the expression of IFN-Л, IL-1p, IL-6, IL-8 and IL-10 genes was revealed. Discussion. We observed the activation of gene expression of IFN-A, IL-1P, IL-6, IL-8 and suppression of IL-10 gene activity when treatment CA of LB cells.

Conclusion. The substance CA has new effects on the activation of the expression of a number of key cytokine genes in stable Burkitt lymphoma cell lines.

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29. Akdis M., Aab A., Altunbulakli C., Azkur K. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor P, and TNF-a: Receptors, functions, and roles in diseases. JACI. 2016; 138(4): 984-1010. Doi: https://doi.org/10.1016/jjaci.2016.06.033

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