ArticlePloS one2016
Poly(I:C) Induces Human Lung Endothelial Barrier Dysfunction by Disrupting Tight Junction Expression of Claudin-5.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
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- Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection.Viruses · 2022Article
- Blood-Brain Barrier in Brain Tumors: Biology and Clinical Relevance.International journal of molecular sciences · 2021Review
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- A thrombin-PAR1/2 feedback loop amplifies thromboinflammatory endothelial responses to the viral RNA analogue poly(I:C).Blood advances · 2021Article
- Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction.Frontiers in cellular neuroscience · 2021Review
- Tight Junction Modulating Bioprobes for Drug Delivery System to the Brain: A Review.Pharmaceutics · 2020Review
- Understanding immunopathological fallout of human coronavirus infections including COVID-19: Will they cross the path of rheumatologists?International journal of rheumatic diseases · 2020Review
- RNA Signaling in Pulmonary Arterial Hypertension-A Double-Stranded Sword.International journal of molecular sciences · 2020Review
- Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection.Frontiers in cell and developmental biology · 2020Review
- Simvastatin ameliorates oxygen glucose deprivation/reoxygenation-induced pulmonary endothelial barrier dysfunction by restoring cell-cell junctions and actin cytoskeleton dynamics via the PI3K/Akt signaling pathway.American journal of translational research · 2020Article
- Toll-like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2019Article
- Different concentrations of lipopolysaccharide regulate barrier function through the PI3K/Akt signalling pathway in human pulmonary microvascular endothelial cells.Scientific reports · 2018Article
- Toll-Like Receptor-3 Mediates HIV-1-Induced Interleukin-6 Expression in the Human Brain Endothelium via TAK1 and JNK Pathways: Implications for Viral Neuropathogenesis.Molecular neurobiology · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral infections are often accompanied by pulmonary microvascular leakage and vascular endothelial dysfunction via mechanisms that are not completely defined. Here, we investigated the effect of the Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA (dsRNA) commonly used to simulate viral infections, on the barrier function and tight junction integrity of primary human lung microvascular endothelial cells. Poly(I:C) stimulated IL-6, IL-8, TNFα, and IFNβ production in conjunction with the activation of NF-κB and IRF3 confirming the Poly(I:C)-responsiveness of these cells. Poly(I:C) increased endothelial monolayer permeability with a corresponding dose- and time-dependent decrease in the expression of claudin-5, a transmembrane tight junction protein and reduction of CLDN5 mRNA levels. Immunofluorescence experiments revealed disappearance of membrane-associated claudin-5 and co-localization of cytoplasmic claudin-5 with lysosomal-associated membrane protein 1. Chloroquine and Bay11-7082, inhibitors of TLR3 and NF-κB signaling, respectively, protected against the loss of claudin-5. Together, these findings provide new insight on how dsRNA-activated signaling pathways may disrupt vascular endothelial function and contribute to vascular leakage pathologies.
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