Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative
Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almo...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/11/1718 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846152303766142976 |
|---|---|
| author | Alexander Narovlyansky Alexander Pronin Vladislav Poloskov Alexander Sanin Marina Mezentseva Irina Fedyakina Irina Suetina Igor Zubashev Felix Ershov Marina Filimonova Valentina Surinova Irina Volkova Egor Bogdanov |
| author_facet | Alexander Narovlyansky Alexander Pronin Vladislav Poloskov Alexander Sanin Marina Mezentseva Irina Fedyakina Irina Suetina Igor Zubashev Felix Ershov Marina Filimonova Valentina Surinova Irina Volkova Egor Bogdanov |
| author_sort | Alexander Narovlyansky |
| collection | DOAJ |
| description | Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors <i>TLR2</i>, <i>TLR3</i>, <i>TLR4</i>, <i>TLR7</i>, <i>TLR8</i>, and <i>TLR9</i> was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the <i>TLR3</i> and <i>TLR4</i> genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (<i>IFNA1</i>, <i>IFNA2</i>, <i>IFNB1</i>, <i>IFNK</i>, and <i>IFNλ1</i>) genes with simultaneous stimulation of the expression of interferon receptor (<i>IFNAR1</i> and <i>IFNAR2</i>) genes and signalling molecule (<i>JAK1</i> and <i>ISG15</i>) genes was detected. Increased fold stimulation of the expression of the cytokine genes <i>IL6</i>, <i>TNFA</i>, <i>IL12A</i>, and <i>IL12B</i> was also observed. Thus, it is shown that the XXV is an activator of <i>TLR</i> genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons. |
| format | Article |
| id | doaj-art-e152eb36ea3a4ec582a4e4bbb1d1bcb0 |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-e152eb36ea3a4ec582a4e4bbb1d1bcb02024-11-26T18:25:25ZengMDPI AGViruses1999-49152024-10-011611171810.3390/v16111718Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid DerivativeAlexander Narovlyansky0Alexander Pronin1Vladislav Poloskov2Alexander Sanin3Marina Mezentseva4Irina Fedyakina5Irina Suetina6Igor Zubashev7Felix Ershov8Marina Filimonova9Valentina Surinova10Irina Volkova11Egor Bogdanov12National Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaNational Research Centre for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya, Ministry of Health of the Russian Federation, Moscow 123098, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk 249036, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk 249036, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk 249036, RussiaFaculty of Biotechnology, Lomonosov Moscow University of Fine Chemical Technology, Moscow 119571, RussiaOngoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors <i>TLR2</i>, <i>TLR3</i>, <i>TLR4</i>, <i>TLR7</i>, <i>TLR8</i>, and <i>TLR9</i> was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the <i>TLR3</i> and <i>TLR4</i> genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (<i>IFNA1</i>, <i>IFNA2</i>, <i>IFNB1</i>, <i>IFNK</i>, and <i>IFNλ1</i>) genes with simultaneous stimulation of the expression of interferon receptor (<i>IFNAR1</i> and <i>IFNAR2</i>) genes and signalling molecule (<i>JAK1</i> and <i>ISG15</i>) genes was detected. Increased fold stimulation of the expression of the cytokine genes <i>IL6</i>, <i>TNFA</i>, <i>IL12A</i>, and <i>IL12B</i> was also observed. Thus, it is shown that the XXV is an activator of <i>TLR</i> genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons.https://www.mdpi.com/1999-4915/16/11/1718indole-3-carboxylic acid derivativemacrophage-like cellsreal-time polymerase chain reactiongene expressiontoll-like receptorscytokines |
| spellingShingle | Alexander Narovlyansky Alexander Pronin Vladislav Poloskov Alexander Sanin Marina Mezentseva Irina Fedyakina Irina Suetina Igor Zubashev Felix Ershov Marina Filimonova Valentina Surinova Irina Volkova Egor Bogdanov Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative Viruses indole-3-carboxylic acid derivative macrophage-like cells real-time polymerase chain reaction gene expression toll-like receptors cytokines |
| title | Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative |
| title_full | Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative |
| title_fullStr | Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative |
| title_full_unstemmed | Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative |
| title_short | Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative |
| title_sort | expression of toll like receptor genes and antiviral cytokines in macrophage like cells in response to indole 3 carboxylic acid derivative |
| topic | indole-3-carboxylic acid derivative macrophage-like cells real-time polymerase chain reaction gene expression toll-like receptors cytokines |
| url | https://www.mdpi.com/1999-4915/16/11/1718 |
| work_keys_str_mv | AT alexandernarovlyansky expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT alexanderpronin expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT vladislavpoloskov expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT alexandersanin expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT marinamezentseva expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT irinafedyakina expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT irinasuetina expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT igorzubashev expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT felixershov expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT marinafilimonova expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT valentinasurinova expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT irinavolkova expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative AT egorbogdanov expressionoftolllikereceptorgenesandantiviralcytokinesinmacrophagelikecellsinresponsetoindole3carboxylicacidderivative |