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High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity

P-glycoprotein (encoded by the ABCB1 gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low leve...

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Autores principales: Pavlova, Ekaterina N., Lepekha, Larisa N., Rybalkina, Ekaterina Yu., Tarasov, Ruslan V., Sychevskaya, Ksenia A., Voronezhskaya, Elena E., Masyutin, Alexander G., Ergeshov, Atadzhan E., Erokhina, Maria V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573207/
https://www.ncbi.nlm.nih.gov/pubmed/37834286
http://dx.doi.org/10.3390/ijms241914839
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author Pavlova, Ekaterina N.
Lepekha, Larisa N.
Rybalkina, Ekaterina Yu.
Tarasov, Ruslan V.
Sychevskaya, Ksenia A.
Voronezhskaya, Elena E.
Masyutin, Alexander G.
Ergeshov, Atadzhan E.
Erokhina, Maria V.
author_facet Pavlova, Ekaterina N.
Lepekha, Larisa N.
Rybalkina, Ekaterina Yu.
Tarasov, Ruslan V.
Sychevskaya, Ksenia A.
Voronezhskaya, Elena E.
Masyutin, Alexander G.
Ergeshov, Atadzhan E.
Erokhina, Maria V.
author_sort Pavlova, Ekaterina N.
collection PubMed
description P-glycoprotein (encoded by the ABCB1 gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of ABCB1 gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of HIF1a, TGM2, IL6, SOCS3, and STAT3, which correlated with high ABCB1 expression. The second signature was characterized by high expression of TNFa and CD163 and low expression of ABCB1. These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment.
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spelling pubmed-105732072023-10-14 High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity Pavlova, Ekaterina N. Lepekha, Larisa N. Rybalkina, Ekaterina Yu. Tarasov, Ruslan V. Sychevskaya, Ksenia A. Voronezhskaya, Elena E. Masyutin, Alexander G. Ergeshov, Atadzhan E. Erokhina, Maria V. Int J Mol Sci Article P-glycoprotein (encoded by the ABCB1 gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of ABCB1 gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of HIF1a, TGM2, IL6, SOCS3, and STAT3, which correlated with high ABCB1 expression. The second signature was characterized by high expression of TNFa and CD163 and low expression of ABCB1. These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment. MDPI 2023-10-02 /pmc/articles/PMC10573207/ /pubmed/37834286 http://dx.doi.org/10.3390/ijms241914839 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pavlova, Ekaterina N.
Lepekha, Larisa N.
Rybalkina, Ekaterina Yu.
Tarasov, Ruslan V.
Sychevskaya, Ksenia A.
Voronezhskaya, Elena E.
Masyutin, Alexander G.
Ergeshov, Atadzhan E.
Erokhina, Maria V.
High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity
title High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity
title_full High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity
title_fullStr High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity
title_full_unstemmed High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity
title_short High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity
title_sort high and low levels of abcb1 expression are associated with two distinct gene signatures in lung tissue of pulmonary tb patients with high inflammation activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573207/
https://www.ncbi.nlm.nih.gov/pubmed/37834286
http://dx.doi.org/10.3390/ijms241914839
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