[塞拉格利普抗病毒药物的干扰素调节活性及其对滤泡性淋巴瘤患者活性氧生成和先天免疫基因表达的影响]

[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].

作者信息

Narovlyansky A N, Poloskov V V, Ivanova A M, Kravchenko S K, Babayeva F E, Sychevskaya K A, Mezentseva M V, Suetina I A, Russu L I, Izmest'eva A V, Ospelnikova T P, Sarymsakov A A, Ershov F I

机构信息

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya.

National Research Center for Hematology.

出版信息

Vopr Virusol. 2020 Nov 15;65(5):284-293. doi: 10.36233/0507-4088-2020-65-5-5.

DOI:10.36233/0507-4088-2020-65-5-5

PMID:33533212

Abstract

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.

摘要

引言

干扰素诱导剂（IFNs）类药物可“开启”1型干扰素（IFN-I）的合成，并诱导干扰素刺激基因（ISGs）的表达，这些基因可调节先天免疫反应，保护宿主免受感染因子和肿瘤病变的侵害。本研究的目的是确定药物塞拉利普（CA）在滤泡性淋巴瘤（FL）患者先天免疫基因激活中的作用以及对活性氧（ROS）产生的影响。

目的

研究用CA制剂治疗FL患者血细胞后ROS的产生强度以及IFN-α2、IFN-λ1、ISG15、BCL2、P53（TP53）和USP18基因的表达水平。

材料与方法

本研究纳入了诊断为滤泡性淋巴瘤（FL）的原发性癌症患者和健康志愿者。对其血细胞中活性氧（ROS）产生动力学进行了分析，并通过实时PCR检测了CA处理后一组基因的表达情况。

结果与讨论

在有CA存在的情况下，FL患者和志愿者血细胞中的ROS产生显著降低（P<0.05）。FL患者组中ISG15、P53（TR53）和USP 18的基因表达水平显著高于志愿者组。在用CA处理血细胞时，根据USP18基因的表达水平，可以将FL患者分为阳性和阴性反应组。在用CA处理血细胞后，我们根据USP18基因的表达水平将FL患者分为阳性和阴性反应组。