KFU. Card publication. Ассоциация полиморфизма bcl1 гена nr3c1 с нарушением программируемой клеточной гибели лимфоцитов больных атопической бронхиальной астмой

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АССОЦИАЦИЯ ПОЛИМОРФИЗМА BCL1 ГЕНА NR3C1 С НАРУШЕНИЕМ ПРОГРАММИРУЕМОЙ КЛЕТОЧНОЙ ГИБЕЛИ ЛИМФОЦИТОВ БОЛЬНЫХ АТОПИЧЕСКОЙ БРОНХИАЛЬНОЙ АСТМОЙ

Form of presentation

Articles in Russian journals and collections

Year of publication

2024

Язык

русский

Authors, employees of KFU

Abramova Zinaida Ivanovna, author

Reshetnikova Irina Dmitrievna, author

Skibo Yuliya Valerevna, author

Authors, students KFU

Bogomazova Arina Alekseevna, author

Bibliographic description in the original language

Bogomazova A. A. Associaciya polimorfizma bcl1 gena nr3c1 s narusheniem programmiruemoy kletochnoy gibeli limfocitov bolnykh atopicheskoy bronkhialnoy astmoy / A. A. Bogomazova, I. D. Reshetnikova, Yu. V. Skibo, Z. I. Abramova // Medicinskaya immunologiya.- 2024.-T: -26, № 3.-S.523-532.

Annotation

Atopic asthma is a chronic disease characterized by airway obstruction, bronchial hyperresponsiveness, and inflammation. Patients show increased activation of immune cells in the airways, especially T-lymphocytes, leading to chronic inflammation. The lymphocytes of asthma patients are known to have an impairment of the type 1 and 2 programmed cell death, i.e., apoptosis and autophagy, thus contributing to prolongation and intensification of inflammatory process. As compared to apoptosis, autophagy may also contribute to cell survival under stress conditions. Its disruption and hyperactivation leads to exacerbation of allergic responses. Glucocorticoids are the main drugs for the treatment of atopic bronchial asthma by activating the glucocorticoid receptor, thus triggering anti-inflammatory response and apoptosis of the cells. However, some patients exhibit resistance to therapy due to various factors, including single nucleotide polymorphisms of NR3C1 glucocorticoid receptor gene. The highest association between asthma severity and resistance to therapy was found for the GG variant of the NR3C1 Bcl1 polymorphism. Common molecular pathways for glucocorticoid receptor activation and programmed cell death and mediating molecules suggest a significant role for the polymorphic receptor variant in cell death. The aim of our study was to evaluate the effect of a single nucleotide polymorphism (G allele, i.e., Bcl1 polymorphism of NR3C1 gene) of glucocorticoid receptor on expression levels of genes that regulate apoptosis (BCL2, CASP3) and autophagy (BECN1, LC3) in lymphocytes of patients with moderate and severe atopic bronchial asthma. The study was performed with peripheral blood samples of 24 patients aged 20 to 45 years with an established diagnosis of moderate to severe atopic bronchial asthma. Using PCR technique with restriction fragment length polymorphism (RFLP) assay, the patients were distributed according to the genotypes of the BclI polymorphism of the NR3C1 gene: 12 patients with CC genotype, 8 persons with GC genotype, and 4 cases with GG genotype. The lymphocytes were isolated in Ficoll density gradient and cultivated with dexamethasone under the conditions of nutrient depletion. The level of gene expression was determined by real-time PCR. When studying associations between various genotypes of Bcl1 polymorphism and expression of cell death marker genes, the anti-apoptotic reactions were detected in lymphocytes of patients with GG polymorphism under the influence of dexamethasone thus being a potential mechanism for development of resistance to glucocorticosteroid therapy in asthma. Impaired activation of BECN1 gene expression in patients with the GG genotype may suggest deregulation of the autophagy in this 525 Bcl1 и гибель лимфоцитов 2024, Vol. 26, 3 NR3C1 Bcl1 gene variant and lymphocyte death 2024, Т. 26, № 3 group of patients, as a mode of programmed cell death. Moreover, in patients with GC genotype during longterm cultivation,

Keywords

bronchial asthma, lymphocytes, glucocorticoid receptor, resistance, polymorphism, apoptosis, autophagy

The name of the journal

Медицинская иммунология

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85192499079&doi=10.15789%2f1563-0625-AON-2908&partnerID=40&md5=958c2a3a5187e5c8e72b3ec2230bbb61

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=298792&p_lang=2

Resource files

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Full metadata record

Field DC	Value	Language
dc.contributor.author	Abramova Zinaida Ivanovna	ru_RU
dc.contributor.author	Reshetnikova Irina Dmitrievna	ru_RU
dc.contributor.author	Skibo Yuliya Valerevna	ru_RU
dc.contributor.author	Bogomazova Arina Alekseevna	ru_RU
dc.date.accessioned	2024-01-01T00:00:00Z	ru_RU
dc.date.available	2024-01-01T00:00:00Z	ru_RU
dc.date.issued	2024	ru_RU
dc.identifier.citation	Богомазова А. А. Ассоциация полиморфизма bcl1 гена nr3c1 с нарушением программируемой клеточной гибели лимфоцитов больных атопической бронхиальной астмой / А. А. Богомазова, И. Д. Решетникова, Ю. В. Скибо, З. И. Абрамова // Медицинская иммунология.- 2024.-Т: -26, № 3.-С.523-532.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=298792&p_lang=2	ru_RU
dc.description.abstract	Медицинская иммунология	ru_RU
dc.description.abstract	Atopic asthma is a chronic disease characterized by airway obstruction, bronchial hyperresponsiveness, and inflammation. Patients show increased activation of immune cells in the airways, especially T-lymphocytes, leading to chronic inflammation. The lymphocytes of asthma patients are known to have an impairment of the type 1 and 2 programmed cell death, i.e., apoptosis and autophagy, thus contributing to prolongation and intensification of inflammatory process. As compared to apoptosis, autophagy may also contribute to cell survival under stress conditions. Its disruption and hyperactivation leads to exacerbation of allergic responses. Glucocorticoids are the main drugs for the treatment of atopic bronchial asthma by activating the glucocorticoid receptor, thus triggering anti-inflammatory response and apoptosis of the cells. However, some patients exhibit resistance to therapy due to various factors, including single nucleotide polymorphisms of NR3C1 glucocorticoid receptor gene. The highest association between asthma severity and resistance to therapy was found for the GG variant of the NR3C1 Bcl1 polymorphism. Common molecular pathways for glucocorticoid receptor activation and programmed cell death and mediating molecules suggest a significant role for the polymorphic receptor variant in cell death. The aim of our study was to evaluate the effect of a single nucleotide polymorphism (G allele, i.e., Bcl1 polymorphism of NR3C1 gene) of glucocorticoid receptor on expression levels of genes that regulate apoptosis (BCL2, CASP3) and autophagy (BECN1, LC3) in lymphocytes of patients with moderate and severe atopic bronchial asthma. The study was performed with peripheral blood samples of 24 patients aged 20 to 45 years with an established diagnosis of moderate to severe atopic bronchial asthma. Using PCR technique with restriction fragment length polymorphism (RFLP) assay, the patients were distributed according to the genotypes of the BclI polymorphism of the NR3C1 gene: 12 patients with CC genotype, 8 persons with GC genotype, and 4 cases with GG genotype. The lymphocytes were isolated in Ficoll density gradient and cultivated with dexamethasone under the conditions of nutrient depletion. The level of gene expression was determined by real-time PCR. When studying associations between various genotypes of Bcl1 polymorphism and expression of cell death marker genes, the anti-apoptotic reactions were detected in lymphocytes of patients with GG polymorphism under the influence of dexamethasone thus being a potential mechanism for development of resistance to glucocorticosteroid therapy in asthma. Impaired activation of BECN1 gene expression in patients with the GG genotype may suggest deregulation of the autophagy in this 525 Bcl1 и гибель лимфоцитов 2024, Vol. 26, 3 NR3C1 Bcl1 gene variant and lymphocyte death 2024, Т. 26, № 3 group of patients, as a mode of programmed cell death. Moreover, in patients with GC genotype during longterm cultivation,	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	bronchial asthma	ru_RU
dc.subject	lymphocytes	ru_RU
dc.subject	glucocorticoid receptor	ru_RU
dc.subject	resistance	ru_RU
dc.subject	polymorphism	ru_RU
dc.subject	apoptosis	ru_RU
dc.subject	autophagy	ru_RU
dc.title	Ассоциация полиморфизма bcl1 гена nr3c1 с нарушением программируемой клеточной гибели лимфоцитов больных атопической бронхиальной астмой	ru_RU
dc.type	Articles in Russian journals and collections	ru_RU