The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sjögren’s syndrome

Arthritis Research & Therapy, Journal Year: 2022, Volume and Issue: 24(1)

Published: July 19, 2022

Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases; however, their roles primary Sjögren's syndrome (pSS) remain unclear. We aimed to reveal potential neutrophils neutrophil extracellular traps (NETs) pSS.pSS patients were enrolled markers measured plasma labial glands using ELISA immunofluorescence. The gene signatures assessed by RNA-Seq RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (MitoSOX) production, JC-1 flow cytometry.NETosis including cell-free DNA (cf-DNA) myeloperoxidase (MPO) from pSS significantly higher than healthy controls (HCs) associated with disease activity. RNA sequencing RT-qPCR revealed activated type I IFN signaling pathway expression genes related interferon neutrophils. Further stimulating IFN-α 2a vitro induced production monomer percentage neutrophils.Our data suggest involvement enhanced patients. mechanism study that activation led damage which finally result generation NETs.

Language: Английский

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The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: April 28, 2023

The recognition of viral nucleic acids by host pattern receptors (PRRs) is critical for initiating innate immune responses against infections. These are mediated the induction interferons (IFNs), IFN-stimulated genes (ISGs) and pro-inflammatory cytokines. However, regulatory mechanisms to avoid excessive or long-lasting that may cause detrimental hyperinflammation. Here, we identified a novel function ISG, IFN alpha inducible protein 27 (IFI27) in counteracting triggered cytoplasmic RNA binding. Our model systems included three unrelated infections caused Influenza A virus (IAV), Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), Sendai (SeV), transfection with an analog double-stranded (ds) RNA. Furthermore, found IFI27 has positive effect on IAV SARS-CoV-2 replication, most likely due its ability counteract host-induced antiviral responses, including vivo . We also show interacts PRR retinoic acid-inducible gene I (RIG-I), being interaction RIG-I through Interestingly, our results indicate impairs activation, providing molecular mechanism modulating responses. study identifies explain counterbalancing preventing Therefore, this will have important implications drug design control viral-induced pathology.

Language: Английский

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Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: May 15, 2019

Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the lymph node. Chronic disease is associated with increased inflammation cell infiltrate. However, it currently unknown if or how respond to infiltrate during chronic disease. Here we demonstrate that vessel abundance increases patients areas of fibrosis infiltration. Using single-cell mRNA sequencing multi-spectral immunofluorescence analysis identified endothelial found results (LECs) are active cycle expression CCL21. Additionally, LECs from NASH adopt a transcriptional program IL13 signaling. Moreover, oxidized low density lipoprotein, pathogenesis, induced transcription protein production both vitro mouse model. Finally, show lipoprotein reduced PROX1 decreased stability. Together these data indicate participants liver, expanding an attempt maintain tissue homeostasis. when inflammatory signals, such as increased, NASH, declines homeostasis impeded.

Language: Английский

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Pseudomonas aeruginosa outer membrane vesicle-packed sRNAs can enter host cells and regulate innate immune responses

Microbial Pathogenesis, Journal Year: 2024, Volume and Issue: 188, P. 106562 - 106562

Published: Feb. 1, 2024

Language: Английский

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Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1011954 - e1011954

Published: Feb. 1, 2024

Epstein-Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus that causally associated with several malignancies. In addition to latent factors, lytic replication contributes cancer development. this study, we examined whether the gene BNRF1, which conserved among gamma-herpesviruses, has an important role in lymphomagenesis. We found lymphoblastoid cell lines (LCLs) established by BNRF1-knockout EBV exhibited remarkably lower pathogenicity mice xenograft model than LCLs produced wild-type (LCLs-WT). RNA-seq analyses revealed BNRF1 elicited expression of interferon-inducible protein 27 (IFI27), promotes proliferation. IFI27 knockdown LCLs-WT resulted excessive production reactive oxygen species, leading death and significantly decreased their vivo . also confirmed was upregulated during primary infection B-cells. Our findings promoted robust proliferation B-cells were transformed via upregulation both vitro

Language: Английский

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Pathways to Severe COVID‐19 for People with Obesity

Obesity, Journal Year: 2020, Volume and Issue: 29(4), P. 645 - 653

Published: Dec. 3, 2020

Increased morbidity and mortality from coronavirus disease 2019 (COVID-19) in people with obesity have illuminated the intersection of impaired responses to infections. Although data on mechanisms by which COVID-19 impacts health are being rapidly generated, there is a critical need better understand pulmonary, vascular, metabolic, immunologic aspects that drive increased risk for complications obesity. This review provides broad overview between physiology order highlight potential severity identify areas future investigation toward developing tailored therapy who develop COVID-19.

Language: Английский

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SARS-CoV-2 Achieves Immune Escape by Destroying Mitochondrial Quality: Comprehensive Analysis of the Cellular Landscapes of Lung and Blood Specimens From Patients With COVID-19

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

Published: July 1, 2022

Mitochondria get caught in the crossfire of coronavirus disease 2019 (COVID-19) and antiviral immunity. The mitochondria-mediated immunity represents host’s first line defense against viral infection, mitochondria are important targets COVID-19. However, specific manifestations mitochondrial damage patients with COVID-19 have not been systematically clarified. This study comprehensively analyzed one single-cell RNA-sequencing dataset lung tissue two bulk datasets blood from patients. We found significant changes mitochondrion-related gene expression, functions, related metabolic pathways SARS-CoV-2 infected host alveolar epithelial cells, which may induced excessive fission, inhibited degradation, destroyed calcium uniporter (MCU). type II cell count decreased transformation to I cells was blocked, exacerbated immune escape replication Subsequently, macrophages phagocytized respiratory capacity activated ROS–HIF1A pathway macrophages, thereby aggravating pro-inflammatory reaction lungs. Infected released large amounts interferon into blood, activating IFI27 expression destroying energy metabolism cells. plasma differentiation B lung-blood interaction regulatory T (Tregs) exacerbated, resulting a cytokine storm inflammation. Thus, our findings explain inflammation seen during perspective quality imbalance.

Language: Английский

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IFI27 Integrates Succinate and Fatty Acid Oxidation to Promote Adipocyte Thermogenic Adaption

Advanced Science, Journal Year: 2023, Volume and Issue: 10(28)

Published: Aug. 6, 2023

Mitochondria are the pivot organelles to control metabolism and energy homeostasis. The capacity of mitochondrial metabolic adaptions cold stress is essential for adipocyte thermogenesis. How brown adipocytes keep fitness upon a challenge cold-induced oxidative has not been well characterized. This manuscript shows that IFI27 plays an important role in cristae morphogenesis, keeping intact succinate dehydrogenase (SDH) function active fatty acid oxidation sustain thermogenesis adipocytes. protein interaction map identifies SDHB HADHA as its binding partners. physically links chaperone TNF receptor associated 1 (TRAP1), which shields from damage-triggered degradation. Moreover, increases hydroxyacyl-CoA trifunctional multienzyme complex subunit alpha (HADHA) catalytic activity β-oxidation pathway. reduced SDH level Ifi27-knockout fat results impaired oxygen consumption defective Thus, novel regulator

Language: Английский

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Effects of Genistein on Differentiation and Viability of Human Visceral Adipocytes

Nutrients, Journal Year: 2018, Volume and Issue: 10(8), P. 978 - 978

Published: July 27, 2018

Obesity can lead to pathological growth of adipocytes by inducing inflammation and oxidative stress. Genistein could be a potential candidate for the treatment obesity due its antioxidant properties. Specific kits were used examine effects genistein vs adiponectin on human visceral pre-adipocytes differentiation, cell viability, mitochondrial membrane potential, stress in white/brown adipocytes. Western Blot was performed changes protein activation/expression. increased differentiation browning, caused dose-related improvement viability potential. Similar observed brown white adipocytes, although cells increase inversely related dose. Moreover, potentiated AMP-activated kinase (AMPK)/mitofusin2 activation/expression protected them from hydrogen peroxide. The similar those adiponectin. results obtained showed that increases against through mechanisms AMPK-signalling keeping function.

Language: Английский

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Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules

Reproductive Biology and Endocrinology, Journal Year: 2021, Volume and Issue: 19(1)

Published: Feb. 23, 2021

Abstract To enhance understanding of polycystic ovary syndrome (PCOS) at the molecular level; this investigation intends to examine genes and pathways associated with PCOS by using an integrated bioinformatics analysis. Based on expression profiling high throughput sequencing data GSE84958 derived from Gene Expression Omnibus (GEO) database, differentially expressed (DEGs) between samples normal controls were identified. We performed a functional enrichment A protein-protein interaction (PPI) network, miRNA- target TF - gene networks, constructed visualized, which hub nodes Validation was receiver operating characteristic (ROC) RT-PCR. Small drug molecules predicted docking. total 739 DEGs identified, 360 up regulated 379 down regulated. GO analysis revealed that mainly involved in peptide metabolic process, organelle envelope RNA binding significantly enriched plasma membrane bounded cell projection organization, neuron DNA-binding transcription factor activity, polymerase II-specific. REACTOME pathway translation respiratory electron transport generic transmembrane small molecules. The top 10 (SAA1, ADCY6, POLR2K, RPS15, RPS15A, CTNND1, ESR1, NEDD4L, KNTC1 NGFR) identified PPI miRNA network network. modules showed electrons signaling NGF, respectively. find series crucial along most closely related initiation advancement. Our investigations provide more detailed mechanism for progression PCOS, detail information potential biomarkers therapeutic targets.

Language: Английский

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