Effect of local suppression of Stat3 gene expression in a mouse model of pulmonary neutrophilic inflammation

Nikolskii, A.A.; Shilovskiy, Igor; Yumashev, K.V.; Vishniakova, L.I.; Barvinskaia, E.D.; Kovchina, V.I.; Korneev, A.V.; Turenko, V.N.; Kaganova, M.M.; Brylina, V.E.; Nikonova, Alexandra; Kozlov, I.B.; Кофиади, И.А.; Sergeev, I.V.; Maerle, Artem; Petukhova, O.A.; Kudlаy, D.А.; Khaitov, Musa

doi:10.33029/0206-4952-2021-42-6-600-614

Cited by 7 publications

(2 citation statements)

References 2 publications

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“…It is known that the manifestation of corticoresistant neutrophilic asthma is dominated by the activity of cytokines IL-17A, IL-17F, IL-21, IL-22, and Th17-initiated neutrophilic inflammation, which occurs via the IL-6/STAT3-dependent signaling pathway (and not via IL-4/STAT6 option) [6] . We assumed in asthma patients with CAHR and a mixed pattern of bronchial inflammation, there is a significant activation of the transcription factor NF-κB and Th1 of the immune response modulated by IFN-γ signals.…”

Section: Results Of a Cytological Studymentioning

confidence: 99%

“…The priority in the development of neutrophilia and a mixed pattern of bronchial inflammation in asthma is given to increasing the expression of such non-T helper cells (Th) 2 type cytokines such as interleukin (IL)-17 and interferon (IFN)-γ [5] . In particular, the molecular cellular mechanisms of the pathogenesis of neutrophilic inflammation correlate with the activation of the Th17 immune response, which is manifested by a high concentration of IL-17A, IL-17F, and IL-8 in the sputum of patients with severe neutrophilic asthma [6] . Cytokine IFN-γ is an important antiviral defense factor and a specific marker of surface costimulatory molecules on antigen-presenting cells [7] .…”

Section: Introductionmentioning

confidence: 99%

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Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Perelman

Пирогов

Prikhodko

et al. 2022

Frigid Zone Medicine

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Objective To evaluate the inflammatory pattern and the interferon (IFN)-γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1. The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r = −0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.

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Section: Results Of a Cytological Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Perelman

Пирогов

Prikhodko

et al. 2022

Frigid Zone Medicine

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Cell-Penetrating Peptides as Vehicles for Delivery of Therapeutic Nucleic Acids. Mechanisms and Application in Medicine

Timotievich,

Shilovskiy,

Khaitov

2023

Biochemistry Moscow

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Currently, nucleic acid therapeutics are actively developed for the treatment and prophylactic of metabolic disorders and oncological, inflammatory, and infectious diseases. A growing number of approved nucleic acid-based drugs evidences a high potential of gene therapy in medicine. Therapeutic nucleic acids act in the cytoplasm, which makes the plasma membrane the main barrier for the penetration of nucleic acid-based drugs into the cell and requires development of special vehicles for their intracellular delivery. The optimal carrier should not only facilitate internalization of nucleic acids, but also exhibit no toxic effects, ensure stabilization of the cargo molecules, and be suitable for a large-scale and low-cost production. Cell-penetrating peptides (CPPs), which match all these requirements, were found to be efficient and low-toxic carriers of nucleic acids. CPPs are typically basic peptides with a positive charge at physiological pH that can form nanostructures with negatively charged nucleic acids. The prospects of CPPs as vehicles for the delivery of therapeutic nucleic acids have been demonstrated in numerous preclinical studies. Some CPP-based drugs had successfully passed clinical trials and were implemented into medical practice. In this review, we described different types of therapeutic nucleic acids and summarized the data on the use of CPPs for their intracellular delivery, as well as discussed, the mechanisms of CPP uptake by the cells, as understanding of these mechanisms can significantly accelerate the development of new gene therapy approaches.

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Clinical and pathogenetic aspects of neutrophilic bronchial inflammation in asthma patients with cold-induced airway hyperresponsiveness (literature review)

et al. 2023

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The review presents data on the effect of neutrophilic bronchial inflammation on the clinical course, external respiration, and formation of the airway response to cold air in patients with asthma. According to the results of modern studies, activation of the structural and functional state of neutrophils in a mixed inflammatory pattern is associated with an increase in disease severity, more difficult achievement of asthma control, pronounced impairment of bronchial patency due to stimulation of epithelial destruction and remodeling, and development and maintenance of cold-induced airway hyperresponsiveness.The mechanisms activating the Th1 cytokine profile and oxidative and halogenation stress and determining the activity of neutrophils and persistence of chronic inflammation lead to oxidative damage to lung parenchyma and epithelial dysfunction, which contributes to cold-induced bronchoconstriction. Cytolysis and NETosis, acting as alternative pathways of neutrophil death in the airways of asthma patients, are considered in terms of final stages of induced activity of neutrophil lysosomes in the mixed asthma phenotype.

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Effect of local suppression of Stat3 gene expression in a mouse model of pulmonary neutrophilic inflammation

Cited by 7 publications

References 2 publications

Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Cell-Penetrating Peptides as Vehicles for Delivery of Therapeutic Nucleic Acids. Mechanisms and Application in Medicine

Clinical and pathogenetic aspects of neutrophilic bronchial inflammation in asthma patients with cold-induced airway hyperresponsiveness (literature review)

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