Endothelial Cell Permeability and Adherens Junction Disruption Induced by Junín Virus Infection

Lander, Heather M.; Grant, Ashley; Albrecht, Thomas; Hill, Terence E.; Peters, C. J.

doi:10.4269/ajtmh.13-0382

Cited by 23 publications

(21 citation statements)

References 51 publications

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“…muridarum infection. These results imply that TLR3-deficiency leads to a more acute breakdown in the integrity cellular tight junctions (TJs) and/or adherence junctions (AJs) that are known to be affected during cellular invasion by specific viral and bacterial pathogens [34, 36, 37, 40–42]. To ascertain whether the dissimilarity in macromolecular permeability and TER between the wild-type and TLR3-deficient OE cells correlates with a differential regulation in TJ gene expression during Chlamydia infection, we measured gene transcription levels of the candidate TJ proteins by quantitative real-time-PCR (qPCR).…”

Section: Resultsmentioning

confidence: 99%

TLR3 deficiency exacerbates the loss of epithelial barrier function during genital tract Chlamydia muridarum infection

et al. 2019

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ProblemChlamydia trachomatis infections are often associated with acute syndromes including cervicitis, urethritis, and endometritis, which can lead to chronic sequelae such as pelvic inflammatory disease (PID), chronic pelvic pain, ectopic pregnancy, and tubal infertility. As epithelial cells are the primary cell type productively infected during genital tract Chlamydia infections, we investigated whether Chlamydia has any impact on the integrity of the host epithelial barrier as a possible mechanism to facilitate the dissemination of infection, and examined whether TLR3 function modulates its impact.Method of studyWe used wild-type and TLR3-deficient murine oviduct epithelial (OE) cells to ascertain whether C. muridarum infection had any effect on the epithelial barrier integrity of these cells as measured by transepithelial resistance (TER) and cell permeability assays. We next assessed whether infection impacted the transcription and protein function of the cellular tight-junction (TJ) genes for claudins1-4, ZO-1, JAM1 and occludin via quantitative real-time PCR (qPCR) and western blot.ResultsqPCR, immunoblotting, transwell permeability assays, and TER studies show that Chlamydia compromises cellular TJ function throughout infection in murine OE cells and that TLR3 deficiency significantly exacerbates this effect.ConclusionOur data show that TLR3 plays a role in modulating epithelial barrier function during Chlamydia infection of epithelial cells lining the genital tract. These findings propose a role for TLR3 signaling in maintaining the integrity of epithelial barrier function during genital tract Chlamydia infection, a function that we hypothesize is important in helping limit the chlamydial spread and subsequent genital tract pathology.

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Section: Resultsmentioning

confidence: 99%

TLR3 deficiency exacerbates the loss of epithelial barrier function during genital tract Chlamydia muridarum infection

et al. 2019

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“…The junction proteins are essential to regulating the integrity of the endothelial monolayer and playing a dominant role in the stability of endothelial cell contacts. The disruption of junction proteins occurs in the early-stage of vascular enhanced endothelial permeability [ 35 ], which represents one of the initial pathologic processes leading to endothelial dysfunction. In the present study, our data demonstrate that the protein expressions of ZO-1 and VE-Cadherin in RAECs were significantly reduced under high glucose, whereas such decreases were significantly attenuated in simvastatin treatment through NLRP3 inflammasome.…”

Section: Discussionmentioning

confidence: 99%

Protection by simvastatin on hyperglycemia-induced endothelial dysfunction through inhibiting NLRP3 inflammasomes

Phuong

Jin

et al. 2017

Oncotarget

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Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal elements to initiate inflammatory responses and plays an important role in the dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents vascular endothelial dysfunction from inflammasome invasion contributing to reduce cardiovascular risk. However, Whether or not the simvastatin improves vascular endothelial barrier function through inhibiting the activation of NLRP3 inflammasome pathway remains unknown. Here, we explored the role and mechanisms of simvastatin in the activation of NLRP3 inflammasome which are involved in vascular endothelial hyperpermeability causing by the disruption of tight junction protein ZO-1 and adherens junction protein VE-Cadherin, an early initiation of cardiovascular complication. Our results found that high glucose significantly induced the formation and activation of NLRP3 inflammasome through NADPH oxidase-dependent reactive oxygen species (ROS) formation, associated with vascular endothelial hyperpermeability causing by ZO-1 and VE-Cadherin disruption in the rat aortic endothelial cells (RAECs). Simvastatin treatment remarkably abolished vascular endothelial hyperpermeability and enhanced the protein expression of ZO-1 and VE-Cadherin through NLRP3 inflammasome. Mechanistically, the inhibitory role of simvastatin endothelial hyperpermeability is attributed to the decreased release of cytoplasmic high mobility group box protein-1 (HMGB1) derived from endothelial NLRP3 inflammasome activation. We further confirm the protective role of simvastatin on vascular leakage in the heart of diabetic rats injected with Evans blue dye, which was associated with HMGB1 release in the serum. Collectively, the mechanism of simvastatin treatment alleviating vascular endothelial permeability dysfunction may be through inhibiting the NLRP3 inflammasome-dependent HMGB1 release in RAECs.

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“…In addition, JEV also induces microglial activation in the brain (Ghoshal et al, 2007), leading to expression of numerous immune-related proteins such as chemokines methyl-accepting chemotaxis protein (MCP-1), macrophage inflammatory protein 1 (MIP-1α, MIP-1β), RANTES), cytokines (IL-1, IL-6, IL-18, TNF-α), vascular endothelial growth factor (VEGF), lymphotoxin, and multiple matrix metalloproteinases (MMPs) (Banati et al, 1993;Shima et al, 1995;Ubogu et al, 2006). It has been confirmed that high levels of IL-6 and MCP-1 after virus infection led to increased vascular permeability (Lander et al, 2014). Moreover, deformation of TJs and disruption of the BBB due to high levels of IL-6 have been detected in a mouse model of JE (Gupta and Rao, 2011;Yang et al, 2011).…”

Section: Disruption Of Tight Junctions Via Icam-1 and Cinc-1mentioning

confidence: 99%

Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system

et al. 2018

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The blood brain barrier consisting of astrocytes, pericytes and brain microvascular endothelial cells plays a vital role in the pathogenesis of neurotropic viruses by controlling the access of circulating molecules, immune cells or viruses into the central nervous system (CNS). However, this barrier is not impenetrable and neuroviruses have evolved to disrupt and evade it. This review aims to describe the underlying entry mechanisms of several neuroviruses such as (Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), Nipah virus (NiV), Rabies virus (RABV), Herpes simplex virus (HSV) and Human immunodeficiency virus (HIV)) into the CNS through BBB disruption. The mechanisms, through which neurotropic viruses enter the BBB, are being studied and are becoming clearer, however, some aspects still remain unknown. Some of these viruses are able to invade the brain parenchyma by a 'Trojan horse' mechanism, through diapedesis of infected immune cells that either cross the BBB paracellularly or transcellularly. Important mechanisms of BBB disruption associated with paracellular entry of viruses include alterations in expression or phosphorylation of tight junction proteins, disruption of the basal lamina and disruption of the actin cytoskeleton. In the absence of such mechanisms, indirect effects of viruses on the immune system are likely causes of barrier disruption.

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Endothelial Cell Permeability and Adherens Junction Disruption Induced by Junín Virus Infection

Cited by 23 publications

References 51 publications

TLR3 deficiency exacerbates the loss of epithelial barrier function during genital tract Chlamydia muridarum infection

TLR3 deficiency exacerbates the loss of epithelial barrier function during genital tract Chlamydia muridarum infection

Protection by simvastatin on hyperglycemia-induced endothelial dysfunction through inhibiting NLRP3 inflammasomes

Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system

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