Abstract

Interferons (IFN) and IFN inducers are effective in suppressing viral reproduction and correcting of the innate immunity mechanisms. The aim of the study was to test the hypothesis of the possible involvement of the IFN inducer CelAgrip (CA) as an activator or suppressor of antiviral effects in Burkitt's lymphoma (LB) cell cultures with different ability to produce Epstein-Barr virus antigens (EBV). The kinetic analysis of the dynamics of reactive oxygen species (ROS) production and determination of gene group expression by real-time PCR in response to CA treatment were done in human cell lines LB P3HR-1 and Namalva, spontaneously producing and not producing EBV antigens. When treating CA in Namalva cells, a decrease in the ROS activation index was found; in P3HR-1 cells, an increase was observed. After treatment with CA, there was no reliable activation of the IFN-α, IFN-β and IFN-λ genes in Namalva cells, but the expression of the ISG15 and P53(TP53) genes was increased more than 1200 times and 4.5 times, respectively. When processing the CA of P3HR-1 cells, the expression of IFN-α genes increased by more than 200 times, IFN-λ - 100 times, and the ISG15 gene - 2.2 times. The relationship between IFN-inducing action of CA and the activity of ISG15 and ROS in LB cell cultures producing and not producing EBV antigens is supposed. In Namalva cells that do not produce EBV antigens the treatment of CA results in suppression of ROS generation and activation of the expression of genes ISG15 and P53 (TP53); in P3HR-1 cells producing EBV antigens, the opposite picture is observed - the formation of ROS and the expression of the IFN-α and IFN-λ genes are activated and the activity of the ISG15 and P53 (TP53) genes is suppressed.

Highlights

  • Interferons (IFN) and IFN inducers are effective in suppressing viral reproduction and correcting of the innate immunity mechanisms

  • The aim of the study was to test the hypothesis of the possible involvement of the IFN inducer CelAgrip (CA) as an activator or suppressor of antiviral effects in Burkitt’s lymphoma (LB) cell cultures with different ability to produce Epstein–Barr virus antigens (EBV)

  • The kinetic analysis of the dynamics of reactive oxygen species (ROS) production and determination of gene group expression by real-time PCR in response to CA treatment were done in human cell lines LB P3HR-1 and Namalva, spontaneously producing and not producing EBV antigens

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Summary

ORIGINAL RESEARCH

Наровлянский А.Н.1, Полосков В.В.1, Иванова А.М.1, Мезенцева М.В.1, Суетина И.А.1, Руссу Л.И.1, Челарская Е.С.1, Изместьева А.В.1, Оспельникова Т.П.1, Зубашев И.К.1, Сарымсаков А.А.2, Ершов Ф.И.1. Выполнен кинетический анализ динамики продукции активных форм кислорода (АФК) и определена экспрессия группы генов методом ПЦР в реальном времени в ответ на обработку ЦА. При обработке ЦA клеток Р3НR-1 экспрессия генов IFN-α возрастала более чем в 200 раз, IFN-λ – в 100 раз и гена ISG15 – в 2,2 раза. Участие авторов: формулировка идеи, цели, задач, анализ литературы и экспериментальных данных, обсуждение, написание и оформление – Наровлянский А.Н., Ершов Ф.И., Сарымсаков А.А., Мезенцева М.В.; экспериментальная работа (исследование экспрессии группы генов методом ПЦР в реальном времени), оформление – Полосков В.В., Челарская Е.С., Зубашев И.К.; экспериментальная работа (кинетический анализ динамики продукции АФК), статистическая обработка, оформление – Иванова А.М., Изместьева А.В.; экспериментальная работа (культура клеток, контроль качества) – Суетина И.А., Руссу Л.И., Оспельникова Т.П.

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