SARS-CoV-2 Spike Protein Induces Paracrine Senescence and Leukocyte Adhesion in Endothelial Cells

Journal of Virology, Год журнала: 2021, Номер 95(17)

Опубликована: Июнь 23, 2021

Increased mortality in COVID-19 cases is often associated with microvascular complications. We have recently shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein promotes an inflammatory cytokine interleukin 6 (IL-6)/IL-6R-induced trans signaling response and alarmin secretion. Virus-infected or spike-transfected human epithelial cells exhibited increase senescence, a release of senescence-associated secretory phenotype (SASP)-related molecules. Introduction the bromodomain-containing 4 (BRD4) inhibitor AZD5153 to senescent reversed this effect reduced SASP-related molecule TMNK-1 EAhy926 (representative endothelial cell lines), when were exposed culture medium (CM) derived from A549 expressing SARS-CoV-2 protein. Cells also senescence enhanced p16, p21, β-galactosidase (SA-β-Gal) expression triggered SASP pathways. Inhibition IL-6 by tocilizumab inhibition receptor Bruton's tyrosine kinase (BTK) zanubrutinib, prior exposure CM cells, inhibited p21 p16 induction. observed reactive oxygen species (ROS) CM. ROS generation lines was after treatment zanubrutinib. Cellular increased level adhesion molecules vascular 1 (VCAM-1) intercellular (ICAM-1), which vitro leukocyte attachment potential. function prevented VCAM-1/ICAM-1 attachment. Taken together, we identified supernatant displayed cellular markers, leading adhesion. IMPORTANCE The present study aimed at examining underlying mechanism extrapulmonary manifestations protein-associated pathogenesis, notion infection pulmonary epithelium can lead mediators drive dysfunction. utilized cultured hepatocytes (Huh7.5) pneumocytes (A549) generate conditioned (CM). Endothelial (TMNK-1 EAhy926) treated markers paracrine mode led Overall, link between these responses potential contribution complication productively SARS-CoV-2-infected humans implicated. Furthermore, use inhibitors (BTK, IL-6, BRD4) showed reverse cells. These results may support selection adjunct therapeutic modalities impede SARS-CoV-2-associated pathogenesis.

Язык: Английский

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SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities

Cytokine & Growth Factor Reviews, Год журнала: 2021, Номер 63, С. 44 - 57

Опубликована: Ноя. 15, 2021

Язык: Английский

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Effects of β-Blockers on the Sympathetic and Cytokines Storms in Covid-19

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Ноя. 11, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative virus in the development of disease 2019 (Covid-19) pandemic. Respiratory manifestations SARS-CoV-2 infection such as lung injury (ALI) and distress (ARDS) leads to hypoxia, oxidative stress, sympatho-activation severe cases sympathetic storm (SS). On other hand, an exaggerated immune response invasion may lead uncontrolled release pro-inflammatory cytokine (CS). In Covid-19, there are interactive interactions between CS SS multi-organ failure (MOF). Interestingly, cutting bridge by anti-inflammatory anti-adrenergic agents mitigate complications that induced severely affected Covid-19 patients. The potential mechanisms through different pathways which activate central center carotid bodies chemosensory input cytokines, cross blood-brain barrier activation center. β2-receptors signaling pathway play crucial role production macrophage activation, B-cells for antibodies with inflammation exacerbation. β-blockers have effects reduction cytokines inhibition NF-κB. conclusion, interrupt this interaction several mediators prevention neural-cytokine loop infection. Evidence from study triggers idea future prospective studies confirm management Covid-19.

Язык: Английский

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The Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19

Inflammation, Год журнала: 2022, Номер 45(4), С. 1651 - 1667

Опубликована: Фев. 24, 2022

Язык: Английский

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Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(4), С. 2360 - 2360

Опубликована: Фев. 21, 2022

The review presents the latest data on role of selenium-containing agents in regulation diseases immune system. We mainly considered contributions compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, well selenoproteins selenium nanoparticles defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description available for each above underlying processes with active participation these agents, their therapeutic pharmacological potential, is presented. main purpose this to systematize information, supplemented by obtained our laboratory, important all processes. In addition, presented information makes it possible understand key differences action compounds, depending chemical physical properties, which obtaining a holistic picture prospects creating drugs based them.

Язык: Английский

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Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2

International Journal of Molecular Sciences, Год журнала: 2021, Номер 23(1), С. 280 - 280

Опубликована: Дек. 28, 2021

Viral infections have afflicted human health and despite great advancements in scientific knowledge technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need review evidence impact of nutritional strategies maintain healthy immune system, particularly instances where there are limited therapeutic treatments. Selenium, an essential trace element humans, long history lowering occurrence severity viral infections. Much benefits derived from selenium due its incorporation into selenocysteine, important component proteins known as selenoproteins. associated with increase reactive oxygen species may result oxidative stress. Studies suggest that deficiency alters response infection by increasing stress rate mutations genome, leading pathogenicity damage host. This examines infections, including novel SARS-CoV-2, context selenium, order inform potential system.

Язык: Английский

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The effects of some essential and toxic metals/metalloids in COVID-19: A review

Food and Chemical Toxicology, Год журнала: 2021, Номер 152, С. 112161 - 112161

Опубликована: Март 29, 2021

Язык: Английский

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Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19

Antioxidants, Год журнала: 2021, Номер 10(9), С. 1341 - 1341

Опубликована: Авг. 25, 2021

Major findings of the pilot study involving 21 critically ill patients during week after admission to critical care unit specialized for COVID-19 are presented. Fourteen have recovered, while seven passed away. There were no differences between them in respect clinical or laboratory parameters monitored. However, protein adducts lipid peroxidation product 4-hydroxynonenal (HNE) higher plasma deceased patients, total antioxidant capacity was below detection limit majority sera samples both groups. Moreover, levels HNE-protein constant survivors, they shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting aggression, which not efficient who died. Immunohistochemistry revealed abundant presence lungs indicating HNE is associated with lethal outcome. It seems spreading from blood vessels more than being a consequence pneumonia. Due limitations relatively small number involved this study, further research on antioxidants needed. This might allow better understanding options utilizing by personalized, integrative biomedicine approach prevent onset HNE-mediated vitious circle aggressive inflammatory diseases.

Язык: Английский

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COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route

Journal of Molecular Neuroscience, Год журнала: 2022, Номер 72(6), С. 1166 - 1181

Опубликована: Март 23, 2022

Язык: Английский

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The Impact of Severe COVID-19 on Plasma Antioxidants

Molecules, Год журнала: 2022, Номер 27(16), С. 5323 - 5323

Опубликована: Авг. 21, 2022

Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate antioxidant signaling plasma eighty-eight patients upon admission Clinical Hospital Dubrava Zagreb, which twenty-two died within a week, while other recovered. The differences between deceased survivors were found, especially reduction superoxide dismutases (SOD-1 SOD-2) activity, was accompanied by alteration glutathione-dependent system intensification thioredoxin-dependent system. Reduced levels non-enzymatic antioxidants, tocopherol, also observed, correlated enhanced (determined 4-hydroxynonenal (4-HNE) neuroprostane levels) modifications proteins assessed as 4-HNE-protein adducts carbonyl groups. These findings confirm onset stress severe SARS-CoV-2, those who from COVID-19, manifested strongly reduced tocopherol level SOD activity associated peroxidation. we propose that preventive and/or supplementary use lipophilic nature, could be beneficial for treatment patients.

Язык: Английский

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