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

Narovlyansky, Alexander N.; Mezentseva, M. V.; Suetina, I. A.; Russu, L. I.; Иванова, А М; Полосков, В. В.; Izmest'eva, A V; Ospelnikova, T P; Sarymsakov, A. A.; Ершов, Ф. И.

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

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…В литературе опубликованы данные о том, что препарат ЦелАгрип (Radiks, Узбекистан), близкий по химическому составу препарату Кагоцел ® , также способен индуцировать гены ИФН и цитокинов в лимфоидных линиях клеток [24,25]. Таким образом, стимуляция препаратом Кагоцел ® экспрессии генов TLR в ТНР-1 моноцитах и генов системы ИФН в клетках различного происхождения согласуются между собой, но нуждаются в подтверждении на модели ТНР-1 моноцитов.…”

Section: результаты и обсуждениеunclassified

The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation

Соколова¹,

Полосков²

2021

Biological Products. Prevention, Diagnosis, Treatment

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Kagocel® is used in Russia for the treatment of viral infections. In terms of its chemical structure, Kagocel® active ingredient is a copolymer of gossypol polyphenol and carboxymethylcellulose. The study investigated antiviral and cytokine-inducing activity of Kagocel®, as well as its toxic effects. The aim of the study was to investigate the effect of Kagoce ® active ingredient on the induction of expression of the innate immune system receptor genes (Toll-like receptors, TLR) in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation. Materials and methods: the effect of Kagocel active ingredient was investigated at the concentrations of 0.2 and 2 mg/mL in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation: non-differentiated monocytes, and monocytes differentiated into macrophage-like cells. Comparative analysis of the activity of TLR 2, 3, 4, 7, 8, 9 genes was carried out by quantitative RT-PCR. The study determined standard deviations of the levels of gene expression in the experimental cells (2deltaCq ± SD) relative to the expression in the control cells. Results: Kagocel active ingredient at the concentration of 0.2 mg/mL induced activation of TLR2 expression in THP-1 monocytes by 3.5 times, TLR3 by 2 times, TLR4 by 1.6 times, and at the concentration of 2 mg/mL also induced activation of TLR7 and TLR8 by 1.4 times, and TLR9 by 2 times. The levels of TLR2, TLR3, TLR9 induction were significantly higher in THP-1 monocytes partially differentiated into macrophage-like cells, and the highest stimulation level was observed for TLR2 (8 times). Conclusions: the results obtained characterise Kagocel® as a stimulator of TLR genes in the THP-1 cell line. The number of TLR genes induced in THP-1 monocytes was shown to increase with the increase in the product concentration. THP-1 monocyte differentiation into macrophage-like cells enhances susceptibility to Kagocel®. The positive regulation of TLR genes activity may account for antiviral and interferon-inducing properties of Kagocel®, and also suggests the possibility of expanding the use of the product for various immune-associated diseases.

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Section: результаты и обсуждениеunclassified

The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation

Соколова¹,

Полосков²

2021

Biological Products. Prevention, Diagnosis, Treatment

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“…В ранее проведённых исследованиях [14] нами было показано, что при обработке ЦА клеток ЛБ наблюдались активация генной экспрессии IFN-λ, интерлейкинов (IL) -1β, -6, -8 и супрессия активности гена IL-10.…”

Section: Introductionunclassified

Interferon-regulating activity of the CelAgrip drug and its influence on the formation of reactive oxygen species and expression of innate immunity genes in Burkitt’s lymphome cell cultures

Narovlyansky¹,

Полосков²,

Иванова³

et al. 2020

Problems of Virology

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Introduction. 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).Material and methods. 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.Results and discussion. 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.Conclusion. 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.

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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

Narovlyansky¹,

Полосков²,

Иванова³

et al. 2020

Voprosy virusologii

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

Cited by 3 publications

References 25 publications

The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation

The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation

Interferon-regulating activity of the CelAgrip drug and its influence on the formation of reactive oxygen species and expression of innate immunity genes in Burkitt’s lymphome cell cultures

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

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