TRANSCRIPTIONAL ACTIVITY OF TLR/RLR RECEPTOR GENES IN MACROPHAGE-LIKE CELLS UNDER THE INFLUENCE OF DRUGS BASED ON ACRIDONEACETIC ACID



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Abstract

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 signaling 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 TLR 2, 3, 4, 7/8, 9 and RIG-I was studied under the influence of the drugs Cycloferon® and Cycloferon L in three concentrations (156, 312 and 625 μg/ml) on 1 hour, 4 hour and 24 hour. 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 TLR 2, 3, 4, 7, 8 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 TLR 2, 3, 4, 7, 8 genes at an exposure period of 24 hours. Hereby, it was shown that the drugs Cycloferon® and Cycloferon L stimulated the expression of the TLR 2, 3, 4, 7, 8 genes (and RIG1 for the drug Cycloferon), which are responsible for the synthesis of innate immune receptors.

About the authors

Alexander Naumovich Narovlyansky

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: narovl@yandex.ru
ORCID iD: 0000-0003-0601-7148
SPIN-code: 9015-5536
Scopus Author ID: 6602895796
ResearcherId: AAI-4691-2020
https://gamaleya.org/about/otdel-interferonov/

Professor, Doctor of Sciences, Biology, 
Head, Department of Interferons;
Head, Laboratory of Cytokines
 
Russian Federation, Gamaleya Str., 18, Moscow, Russia, 123098

Vladislav V. Poloskov

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: en-vladislav@yandex.ru
ORCID iD: 0000-0003-0001-2493
SPIN-code: 1603-6527
http://orcid.org/0000-0003-0001-2493

Researcher, Lab of Cytokines

Russian Federation, 123098, Москва, ул.Гамалеи, 18

Marina V. Mezentseva

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: marmez@mail.ru
ORCID iD: 0000-0001-7346-5536
SPIN-code: 9008-2601
http://orcid.org/0000-0001-7346-5536

Doctor of Biological Sciences, Head of the Laboratory

Russian Federation, 123098, Россия, Москва, ул.Гамалеи, 18

Irina A. Suetina

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: ikas@inbox.ru
ORCID iD: 0000-0003-2878-0590
SPIN-code: 4001-0236
http://orcid.org/0000-0003-2878-0590

Candidate of Biological Sciences, Leading Researcher

Russian Federation, 123098, Россия, Москва, ул. Гамалеи, 18

Andrey V. Tsvetnov

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: marked73@gmail.com

junior researcher

Russian Federation, 123098, Россия, Москва, ул.Гамалеи, 18

Egor Yu. Bogdanov

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: egor.egor.zayats@yandex.ru

research assistant

Russian Federation, 123098, Россия, Москва, ул.Гамалеи, 18

Irina T. Fedyakina

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Email: irfed2@mail.ru

Candidate of Biological Sciences, Leading Researcher, Head of Laboratory

Russian Federation, Gamaleyi St. 18, Moscow, Russian Federation, 123098

Alexey L. Kovalenko

Scientific Advisory Center of Toxicology named after S.N. Golikova Federal Medical-Biological Agency of Russia, St. Petersburg

Email: alleokov@mail.ru
ORCID iD: 0000-0003-3695-2671
SPIN-code: 7216-8364
https://orcid.org/0000-0003-3695-2671

Doctor of Biological Sciences, Leading Researcher

Russian Federation, 192019, St. Petersburg, st. Bekhtereva, 1

Felix I. Ershov

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow

Author for correspondence.
Email: felixershov@gmai.com
ORCID iD: 0000-0002-4780-7560
SPIN-code: 3076-4864
http://orcid.org/0000-0002-4780-7560

Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Chief Researcher

Russian Federation, 123098, Россия, Москва, ул.Гамалеи, 18

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Copyright (c) Narovlyansky A., Poloskov V., Mezentseva M., Suetina I., Tsvetnov A., Bogdanov E., Fedyakina I., Kovalenko A., Ershov F.

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