SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 15, 2024

Abstract Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element human tissues reservoirs is the main product of mRNA COVID-19 vaccines. We investigated whether alone triggers pro-inflammatory pro-coagulant responses primary cultures two cell types deeply affected by SARS-CoV-2, such monocytes cells. Methods In umbilical vein cells (HUVEC) monocytes, components NF-κB NLRP3 inflammasome system, well coagulation regulators, were assessed qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results activated NF-κB, promoted cytokines release, triggered priming activation system resulting mature IL-1β formation both types. This was paralleled enhanced production factors von Willebrand factor (vWF), VIII tissue factor, that mediated, at least part, IL-1β. Additionally, failed to enhance ADAMTS-13 levels counteract activity vWF multimers. Monocytes HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches gene silencing showed TLR4 receptors mediated effects but not HUVEC. Conclusion behaves a stimulus Interfering with signaling pathways evoked may help preventing immune vascular complications driven viral element.

Language: Английский

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SARS-CoV-2 spike protein receptor binding domain promotes IL-6 and IL-8 release via ATP/P2Y2 and ERK1/2 signaling pathways in human bronchial epithelia

Molecular Immunology, Journal Year: 2024, Volume and Issue: 167, P. 53 - 61

Published: Feb. 14, 2024

Language: Английский

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Activation of TLR4 by viral glycoproteins: A double-edged sword?

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 29, 2022

Recognition of viral infection by pattern recognition receptors is paramount for a successful immune response to infection. However, an unbalanced proinflammatory can be detrimental the host. Recently, multiple studies have identified that SARS-CoV-2 spike protein activates Toll-like receptor 4 (TLR4), resulting in induction cytokine expression. Activation TLR4 glycoproteins has also been observed context other models, including respiratory syncytial virus (RSV), dengue (DENV) and Ebola (EBOV). mechanisms involved virus-TLR4 interactions remained unclear. Here, we review act as pathogen-associated molecular patterns induce via TLR4. We explore current understanding underlying how are recognized discuss contribution activation pathogenesis. identify contentious findings research gaps highlight importance glycoprotein-mediated potential therapeutic approaches.

Language: Английский

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Changes in Symptoms Experienced by SARS-CoV-2-Infected Individuals – From the First Wave to the Omicron Variant

Frontiers in Virology, Journal Year: 2022, Volume and Issue: 2

Published: July 1, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and public health crisis since the beginning of 2020. First recognized for induction disease, virus also causes asymptomatic infections or with mild symptoms that can resemble common colds. To provide better understanding these SARS-CoV-2 to monitor development over time, we performed detailed analysis self-reported positive negative individuals. In an online-based survey, total 2117 individuals provided information on associated infection, 1925 participants had tested 192 negative. reported most frequently during early phases by infected were tiredness, headache, impairment smell taste dry cough. With spread alpha delta variants, frequency nose such as blocked runny sneezing increased being almost 60% Interestingly, omicron variant brought sharp decrease in incidence impaired sense taste, which was only 24% this phase pandemic. constellation should be monitored closely months ahead, future variants are likely bring about more changes.

Language: Английский

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Vaccination after developing long COVID: Impact on clinical presentation, viral persistence, and immune responses

International Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 136, P. 136 - 145

Published: Sept. 17, 2023

Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of vaccination on evolution symptoms, immune responses, and viral persistence is unclear.In this prospective observational cohort study, we evaluated number PCC affected organ systems, psychological well-being scores before after patients received vaccination. We simultaneously biomarkers systemic inflammation levels plasma cytokines/chemokines. measured intracellular SARS-CoV-2 antigens, immunoreactivity to antigens in blood.COVID-19 was associated decreases symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 4.02; P <0.001) systems 3.19 1.04 1.89 1.12; <0.001), increases World Health Organization (WHO)-5 Well-Being Index Scores 42.67 22.76 56.15 22.83; <0.001). Patients also had significantly decreased several pro-inflammatory cytokines/chemokines including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1β, stem cell (SCF). participants presented a certain level toward SARS-CoV-2, that boosted S1 antigen persisted blood participants, mostly non-classical monocytes, regardless receiving vaccination.Our study shows higher responses brings forward possible role for mitigating by decreasing inflammation. observed products independent could be involved perpetuating through monocytes.

Language: Английский

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Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway

Nutrients, Journal Year: 2022, Volume and Issue: 14(13), P. 2738 - 2738

Published: June 30, 2022

Black rice is a functional food that high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties exhibit range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses targeting lung tissue innate immune cells during COVID-19 infection long-COVID phenomenon. Our objectives focused health benefits P3G-rich fraction black germ bran (BR extract) inhibition induced by SP, as well NF-kB activation NLRP3 inflammasome pathway an vitro model. In this study, BR extract was identified active anthocyanins, P3G, using HPLC technique. A549-lung differentiated THP-1 macrophages were treated with extract, C3G, or P3G prior exposure 100 ng/mL SP. Their anti-inflammatory then determined. at concentrations 12.5−100 μg/mL exhibited anti-inflammation activity both A549 through significant suppression NLRP3, IL-1β, IL-18 gene expressions IL-6, cytokine secretions dose-dependent manner (p < 0.05). determined cell lines, (at 1.25−10 μg/mL), compatibly responsible SP-induced protein levels With regard mechanism, could attenuate inflammation via counteraction downregulation inflammasome-dependent proteins (NLRP3, ASC, capase-1). Overall, protective anthocyanins obtained from can be employed potentially preventive strategies use pigmented against long-term sequelae infection.

Language: Английский

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Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause post-acute sequelae after infection or COVID-19 vaccination. vaccines utilize modified, stabilized prefusion that may share similar toxic effects with its viral counterpart. aim this study is investigate mechanisms harm biological systems from vaccine-encoded propose mitigation strategies. We searched PubMed, Google Scholar, ‘grey literature’ find studies (1) investigated the on systems, (2) helped differentiate between vaccine-generated proteins, (3) identified detoxification protocols compounds had signals benefit acceptable safety profiles. abundant evidence damage in cardiovascular, hematological, neurological, respiratory, gastrointestinal, immunological systems. Viral proteins have shown play direct role cardiovascular thrombotic injuries both Detection for at least 6-15 months vaccination those indicates as primary contributing factor long COVID. rationalized these findings give support potential long-term post-infection and/or vaccine-induced complications. base protocol, composed oral nattokinase, bromelain, curcumin. This approach holds immense promise clinical care, upon which additional therapeutic agents are applied goal aiding resolution Large-scale, prospective, randomized, double-blind, placebo-controlled trials warranted order determine relative risks benefits protocol.

Language: Английский

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Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages

Viruses, Journal Year: 2023, Volume and Issue: 15(3), P. 754 - 754

Published: March 15, 2023

Critically ill COVID-19 patients display signs of generalized hyperinflammation. Macrophages trigger inflammation to eliminate pathogens and repair tissue, but this process can also lead hyperinflammation resulting exaggerated disease. The role macrophages in dysregulated during SARS-CoV-2 infection is poorly understood. We inoculated treated human macrophage cell line THP-1 with purified, glycosylated, soluble spike protein S1 subunit (S1) clarify the pro-inflammatory responses. Soluble upregulated TNF-α CXCL10 mRNAs, induced secretion from macrophages. While did not support productive replication or viral entry, virus exposure resulted upregulation both genes. Our study shows that extracellular a key component inducing responses macrophages, independent replication. Thus, virus- S1-activated may become sources mediators contributing patients.

Language: Английский

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SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production

iScience, Journal Year: 2023, Volume and Issue: 26(6), P. 106954 - 106954

Published: May 25, 2023

Neurological complications that occur in SARS-CoV-2 infection, such as olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, are thought to contribute long COVID. However, autopsies of patients who have died from COVID-19, there is normally no direct evidence central nervous system damage due proliferation SARS-CoV-2. For this reason, many aspects the pathogenesis mechanisms symptoms remain unknown. Expressing S1 protein nasal cavity mice was associated with increased apoptosis decreased intracerebral acetylcholine production. The decrease production clinical signs, expression cytokine degrading factor ZFP36. Administering cholinesterase inhibitor donepezil improved malaise signs. These findings could elucidation neurological COVID-19

Language: Английский

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Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 111, P. 259 - 269

Published: April 27, 2023

Language: Английский

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