ВЛИЯНИЕ ДЕКСАМЕТАЗОНА НА РЕГУЛЯЦИЮ ПРОГРАММИРУЕМОЙ КЛЕТОЧНОЙ ГИБЕЛИ ЛИМФОЦИТОВ БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ

 

Таким образом, данная работа демонстрирует различия в ответе лимфоцитов больных и здоровых доноров на терапию синтетическими глюкокортикоидами, а также указывает на нарушение регуляции 1 и 2 типа ПКГ лимфоцитов у пациентов с астмой под

воздействием дексаметазона. Несмотря на противоречивость современных данных о влиянии аутофагии иммунных клеток на аллергическое воспаление [2], результаты подтверждают ее значимость в патогенезе заболевания.

 

Работа выполнена за счет средств субсидии, выделенной в рамках государственной поддержки Казанского (Приволжского) федерального университета в целях повышения его конкурентоспособности среди ведущих мировых научно-образовательных центров «Приоритет 2030»

 

Список литературы:

[1] Ichimiya T., Yamakawa T., Hirano T., Yokoyama Y., Hayashi Y., Hirayama D., и др. Autophagy and Autophagy-Related Diseases: A Review // Int J Mol Sci. 2020; Vol. 21 N 23 P. 8974 doi:10.3390/ijms21238974

[2] Ban G., Pham D., Trinh T., Lee S., Suh D., Yang E. Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target // Clinical & Experimental Allergy. 2015; Vol. 46 N 1 P. 48-59. doi:10.1111/cea.12585

 

Автор, ответственный за переписку:

Богомазова Арина Алексеевна; Казанский (Приволжский) федеральный университет; адрес: Россия, 420008, Казань, ул. Кремлевская, 18; лаборант-исследователь; e-mail: arnbgmz @ yandex . ru ; телефон: +79393960098;

 

Соавторы:

Скибо Юлия Валерьевна; Казанский (Приволжский) федеральный университет; адрес: Россия, 420008, Казань, ул. Кремлевская, 18; старший научный сотрудник; кандидат биологических наук; телефон: +7988 833-66-80; e-mail: yuliya_ksu@mail.ru

Абрамова Зинаида Ивановна; Казанский (Приволжский) федеральный университет; адрес: Россия, 420008, Казань, ул. Кремлевская, 18; главный научный сотрудник; доктор биологических наук, профессор; e-mail: Zinaida.Abramova@kpfu.ru

Решетникова Ирина Дмитриевна; Казанский (Приволжский) федеральный университет; адрес: Россия, 420012, Казань, ул. Волкова, 18; доцент кафедры внутренних болезней; кандидат медицинских наук; e-mail: reshira@mail.ru; телефон: +7 903 305-18-16

 

DEXAMETHASONE EFFECTS ON THE REGULATION OF PROGRAMMED CELL DEATH OF LYMPHOCYTES IN PATIENTS WITH BRONCHIAL ASTHMA

Bogomazova A. A., Skibo Y.V., Abramova Z. I., Reshetnikova I. D.

Kazan (Volga Region) Federal University, Kazan, Russia

 

Atopic asthma is a chronic disease characterized by airway obstruction, bronchial hyper-responsiveness, and increased activation of immune cells, especially T lymphocytes, leading to chronic inflammation. It is known that lymphocytes of patients with asthma have an impaired

response to programmed cell death (PCD) types 1 and 2 – apoptosis and autophagy, which contributes to the prolongation and intensification of the inflammatory process. Compared to apoptosis, autophagy can also promote cell survival under stress conditions, and its disruption

and hyperactivation lead to aggravation of allergic reactions [1]. The main therapy used for bronchial asthma are glucocorticoids, which activate the glucocorticoid receptor and triggers an anti-inflammatory response in the cell and apoptosis. Despite the proven influence of PCG

disruption on the course of bronchial asthma, the effect of synthetic glucocorticoids on autophagy has not yet been studied. Therefore, the purpose of the work is to characterize the effect of dexamethasone on the regulation of programmed cell death of lymphocytes in patients

with moderate and severe forms of atopic bronchial asthma.

 

The study was performed on peripheral blood samples from 24 patients aged 20 to 45 years with a confirmed diagnosis of moderate and severe atopic bronchial asthma and 9 healthy donors. The lymphocyte fraction was isolated on a Ficoll density gradient and cultured with and

without the addition of dexamethasone under nutrient depletion conditions for 0 days and 6 days. Morphological markers of PCG after cultivation were detected using transmission electron microscopy. Propidium iodide staining, and subsequent flow cytometry analysis were used to

determine cell cycle parameters. The expression level of the genes BECN1, LC3, CASP3, BCL2 was determined by real-time PCR.

 

Transmission electron microscopy showed that with short-term cultivation without dexamethasone morphological markers of autophagy are more pronounced in patients with bronchial asthma, and with long-term cultivation with dexamethasone the main markers of apoptosis were observed in patients. Analysis of cell cycle parameters showed a statistically significant increase in the number of cells in the G0/G1 phase after 2 hours of cultivation under the influence of dexamethasone in patients with bronchial asthma. According to the results of the study, during long-term cultivation the expression of the BECN1 gene in healthy donors increased under the influence of dexamethasone, while in the group of patients with asthma the expression level remained unchanged. Expression of the LC3 gene, a major marker of autophagy, was increased by dexamethasone compared to untreated lymphocytes. Dexamethasone also increased the expression level of BCL2 in both study groups at any time of cultivation. The expression level of the CASP3 gene increased during long-term cultivation with dexamethasone and was significantly higher in patients with asthma than in the control group.

 

Thus, the study demonstrates differences in the response of lymphocytes from healthy donors and patients with asthma to synthetic glucocorticoids and indicates dysregulation of type 1 and type 2 lymphocytes PCG in patients with asthma under the influence of dexamethasone. Despite the contradictory nature of current data on the effect of immune cell autophagy on allergic inflammation [2], the results confirm its importance in the pathogenesis of the disease.

 

The work is carried out in accordance with the Strategic Academic Leadership Program “Priority 2030” of the Kazan Federal University of the Government of the Russian Federation

 

References:

[1] Ichimiya T, Yamakawa T, Hirano T, Yokoyama Y, Hayashi Y, Hirayama D. Autophagy and Autophagy-Related Diseases: A Review. Int J Mol Sci. 2020;21(23):8974. doi:10.3390/ijms21238974