Ambiguity effects of recombinant interferon α2B in an in vitro experiment on the expression of nuclear factor NF-KB, IFNα’βR AND IFNγR (CD119) receptors of neutrophilic granulocytes of patients with chronic herpes virus infections

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Abstract

Introduction. Neutrophil granulocytes (NGs) and the interferon’s system (IFN) play a leading role in antiviral immune defense. At the same time, patients suffering from atypical chronic active herpes-viral infections (ACA-HVI) often have neutropenia and impaired induced IFNα/β and IFNγ production. It is possible that these patients have various disorders of intracellular signaling at all stages of IFNα/β synthesis by immune system cells, including NG, which leads to IFNα/β deficiency. An adequate level of nuclear factor NF-kB expression has positive effects on synthesis of IFNα/β in the last stages of signaling. The disturbances in the expression of NF-kB can lead to defects in the synthesis of IFNα/β.

The aim: to clarify the features of nuclear factor NF-kB, membrane receptors IFNα|βR and IFNγR (CD119) expression on NG of patients with AСA-HVI, with the subsequent assessment of the recombinant IFNα2b (recIFNα2b) effects on them in the experimental system in vitro.

Materials and methods: 25 patients with ACA-HVI of both sexes aged 23-64 years were included in the main group of the study (MSG). In the complex of the study for the detection of herpes-viral infections: the method of serodiagnosis (ELISA), for the detection of the genome of viruses - PCR-RT. 407 blood samples were examined in the in vitro system. Flow cytofluorimetry was used to estimate the amount (%) of NG expressing NF-kB, IFNα|βR, IFNγR, and their expression levels before and after incubation with recIFNα2b. Adequate statistical methods were applied.

Results: In patients suffering from ACA-HVI, a deficiency of induced IFNα and IFNγ production was detected, due to a decrease in the expression density of nuclear factor NF-kB NG, as well as a violation of the expression of membrane receptors IFNα|βR, IFNγR. RecIFNα2b in the in vitro system had a mixed effect on the expression of NF-kB, IFNα|βR and IFNγR NG.

Conclusion: The deficiency of induced IFNα and IFNγ production in patients with ACA-HVI is associated with variable changes in NF-kB, IFNα|βR and IFNγR NG expression. RecIFNα2b in the in vitro system has an ambiguous effect on altered expression of NF-kB, IFNα/β and IFNγ NG, which appears to depend on the innate or adaptive nature of these disorders.

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About the authors

Irina V. Nesterova

The Peoples’ Friendship University of Russia; Kuban state medical university

Email: inesterova1@yandex.ru

doctor of medical sciences, professor, chief of science. department of clinical and experimental immunology and molecular biology, prof. of the department of allergology and immunology

Russian Federation, Moscow; Krasnodar

E. O. Khalturina

I. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: cytokines@yandex.ru

phd, associate professor, associate professor of the department of microbiology, virology and immunology

Russian Federation, Moscow

V. N. Nelyubin

Moscow State University of Medicine and Dentistry

Email: cytokines@yandex.ru

md, professor

Russian Federation, Moscow

S. V. Khaidukov

Shemyakin-Ovchinnikov Institute of bioorganic chemistry

Email: cytokines@yandex.ru

doctor of biological sciences, senior researcher at the carbohydrate laboratory

Russian Federation, Moscow

Galina A. Chudilova

Kuban state medical university

Author for correspondence.
Email: chudilova2015@yandex.ru

doctor of biological sciences, associate professor, head of the department of clinical and experimental immunology and molecular biology, associate professor of clinical immunology, allergology and laboratory diagnostics

Russian Federation, Krasnodar

V. V. Malinovskaya

National Research Centre for Epidemiology and Microbiology N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: cytokines@yandex.ru

professor, head of the laboratory of ontogenesis and correction of the interferon system

Russian Federation, Moscow

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Supplementary files

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2. Рис. 1. Уровни экспрессии по MFI ядерного фактора NF -kB НГ у условно здоровых лиц (ГС) и па- циентов, страдающих АХА-ГВИ (ОГИ). *Достоверность различия между группой сравнения (ГС) и основной группой исследования (ОГИ) при p<0,05

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3. Рис. 2. Сравнение уровней экспрессии по MFI ядерного фактора NF kB НГ пациентов, страдающих АХА-ГВИ, до и после воздействия recIFNα2b в экспе- риментальной системе in vitro. * – достоверность различия между ГС и OГИ; p<0.05. ^^ – достоверность различия между ГС и ГИ1+IFNα2; p<0.05. ^ – достоверность различия между группами исследования ГИ1 и ГИ2 p<0.05. ♦ – достоверность различия между OГИ и ГИ2+IFNα2b; p<0.05.

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4. Рис. 3. Количество НГ, экспрессирующих мембранный рецептор IFNα|βR до и после воздействия recIFNα2b у пациентов, страдающих АГА-ГВИ (в %). ^ – достоверность различия между ГС и ОГИ, p<0.05 * – достоверность различий между ОГИ и ГИ1 после recIFNα2b, p<0.05. ** – достоверность различия между ГС и ГИ2 по- сле recIFNα2b, p<0.05

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5. Рис. 4. Количество НГ, экспрессирующих мем- бранный рецептор IFNγR (СD119) до и после воздей- ствия recIFNα2b у пациентов, страдающих АХА- ГВИ (в %). * – статистически значимые различия по отно- шению к группе сравнения, p<0.05

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6. Таблица 2 Сравнительная характеристика экспрессии ядерного фактора NF-kB, мембранных рецепторов IFNα|βR и IFNγR на НГ условно здоровых лиц и пациентов, страдающих АХА – ГВИ

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7. Таблица 3 Сравнительная характеристика экспрессии ядерного фактора NF-kB, мембранных рецепторов IFNα|βR и CD119 (IFNγR) НГ условно здоровых лиц и пациентов, страдающих АХА – ГВИ до и после воздействия recIFNα2b в эксперименте in vitro

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Copyright (c) 2023 Nesterova I.V., Khalturina E.O., Nelyubin V.N., Khaidukov S.V., Chudilova G.A., Malinovskaya V.V.

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