Transcriptional activity of TLR/RLR receptor genes in macrophage-like cells under the influence of drugs based on acridoneacetic acid
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Published:2024-07-21
Issue:4
Volume:26
Page:663-670
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ISSN:2313-741X
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Container-title:Medical Immunology (Russia)
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language:
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Short-container-title:Med. immunol.
Author:
Narovlyansky A. N.1, Poloskov V. V.1, Mezentseva M. V.1, Suetina I. A.1, Tsvetnov A. V.1, Bogdanov E. Yu.1, Fedyakina I. T.1, Kovalenko A. L.2, Ershov F. I.1
Affiliation:
1. N. Gamaleya National Research Centre for Epidemiology and Microbiology 2. S. Golikov Scientific Advisory Center of Toxicology, Federal Medical-Biological Agency of Russia
Abstract
Activation of Toll-like receptors (TLRs) is one of the earliest indicators of functional activation of the innate immune system. Therefore, the development of drugs that stimulate the transcription of TLR/RLR genes and at the same time are “multi-target” drugs is an important task of modern immunopharmacology. In this regard, antiviral drugs that combine the properties of interferonogens and immunomodulators, which also include Cycloferon® and its analogues, are of great interest. The purpose of this study was to assess the expression of genes that determine the TLR/RLR signalling reactions of the innate immune system under the influence of immunomodulatory antiviral drugs based on acridoneacetic acid (Cycloferon® and Cycloferon L). The study was conducted using a model of immunocompetent cells: THP-1, differentiated by phorbol ester into macrophage-like cells. Gene expression analysis was performed using real-time polymerase chain reaction. The expression level of genes encoding TLR2, TLR3, TLR4, TLR7, TLR8, TLR9 and RIG-I was studied under the influence of the drugs Cycloferon® and Cycloferon L in three concentrations (156 μg/mL, 312 μg/mL and 625 μg/mL) on 1 hour, 4 hours and 24 hours. It was shown that the drug Cycloferon® at concentrations of 156, 312 and 625 μg/mL at 24 hours of exposure dose-dependently stimulated the expression of TLR2, TLR3, TLR4, TLR7, TLR8 receptor genes. A stable stimulation of the expression of RIG1 receptor genes was found upon exposure 4 hours to the drug in all studied concentrations. For the first time, it was revealed that the drug Cycloferon L stimulated a stable increase in the expression of TLR2, TLR3, TLR4, TLR7, TLR8 genes at an exposure period of 24 hours. Hereby, it was shown that the drugs Cycloferon® and Cycloferon L stimulated the expression of the TLR2, TLR3, TLR4, TLR7, TLR8 genes (and RIG1 for the drug Cycloferon), which are responsible for the synthesis of innate immune receptors.
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