Angiopoietin 1 attenuates interleukin-6-induced endothelial cell permeability through SHP-1

Yun, Jeong‐Ho; Han, Man Hyup; Jeong, Han Seok; Lee, Da Hye; Cho, Chung Hyun

doi:10.1016/j.bbrc.2019.08.048

Cited by 12 publications

(9 citation statements)

References 25 publications

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“…23 Among these, IL-6 attracts neutrophils to the injured site, resulting in destruction of endothelial cell integrity. 24 TNF-α interacts with NF-κB to aggravate the inflammatory response. Eventually, a series of damage, such as blood brain barrier destruction, cerebral edema, thrombosis and bleeding, may occur.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

Yang

Zhao

2020

Yonsei Med J

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Purpose: Neonatal hypoxic ischemic encephalopathy (HIE) is an essential factor underlying neonatal death and disability. This study sought to explore the role of miR-146b-5p in regulating neonatal HIE. Materials and Methods: In vitro and in vivo HIE models were established in PC12 cells and 10-day neonatal Sprague Dawley rats, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess miR-146b-5p expression and inflammatory factors [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] in brain lesions and PC12 cells, while enzymelinked immunosorbent assay was employed to detect the expression of oxidative stress factors (SOD and GSH-Px). Gain-and loss-assays of miR-146b-5p were conducted to verify its role in modulating the viability and apoptosis of PC12 cells under oxygenglucose deprivation (OGD) treatment. Expression of TLR4, IRAK1, TRAF6, TAK1, and NF-κB were examined by qRT-PCR and/or Western blot. Dual luciferase activity assay was conducted to identify relationships between miR-146b-5p and IRAK1. Results: In the HIE models, significant oxidative stress and inflammatory responses emerged upon upregulation of TLR4/IRAK1/ TRAF6/TAK1/NF-κB signaling. Overexpression of miR-146b-5p greatly inhibited OGD-induced PC12 cell injury, inflammatory responses, and oxidative stress. Inhibiting miR-146b-5p, however, had the opposite effects. IRAK1 was found to be a target of miR-146b-5p, and miR-146b-5p overexpression suppressed the activation of IRAK1/TRAF6/TAK1/NF-κB signaling. Conclusion: This study demonstrated that miR-146b-5p overexpression alleviates HIE-induced neuron injury by inhibiting the IRAK1/TRAF6/TAK1/NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

Yang

Zhao

2020

Yonsei Med J

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“…IL-6 is a disruptor of endothelial barrier integrity [ 44 , 48 ]. Therefore, the potential contribution of AG490 on endothelial cell permeability was explored in a bEnd.3 endothelial cell model.…”

Section: Resultsmentioning

confidence: 99%

“…The IL-6/Jak2/Stat3 axis has also been implicated in endothelial permeability and poststroke BBB disruption involving the MMP- or ubiquitin proteasome-mediated degradation of tight junction proteins [ 25 , 44 , 48 ]. Rats with cerebral ischemia had decreased endothelial tight junction ZO-1 proteins, which was reversed by AG490 with increased ubiquitin Ubr1 E3 ligase and MMP-9 activity.…”

Section: Discussionmentioning

confidence: 99%

Jak2 Inhibitor AG490 Improved Poststroke Central and Peripheral Inflammation and Metabolic Abnormalities in a Rat Model of Ischemic Stroke

et al. 2021

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Poststroke hyperglycemia and inflammation have been implicated in the pathogenesis of stroke. Janus Kinase 2 (Jak2), a catalytic signaling component for cytokine receptors such as Interleukin-6 (IL-6), has inflammatory and metabolic properties. This study aimed to investigate the roles of Jak2 in poststroke inflammation and metabolic abnormality in a rat model of permanent cerebral ischemia. Pretreatment with Jak2 inhibitor AG490 ameliorated neurological deficit, brain infarction, edema, oxidative stress, inflammation, caspase-3 activation, and Zonula Occludens-1 (ZO-1) reduction. Moreover, in injured cortical tissues, Tumor Necrosis Factor-α, IL-1β, and IL-6 levels were reduced with concurrent decreased NF-κB p65 phosphorylation, Signal Transducers and Activators of Transcription 3 phosphorylation, Ubiquitin Protein Ligase E3 Component N-Recognin 1 expression, and Matrix Metalloproteinase activity. In the in vitro study on bEnd.3 endothelial cells, AG490 diminished IL-6-induced endothelial barrier disruption by decreasing ZO-1 decline. Metabolically, administration of AG490 lowered fasting glucose, with improvements in glucose intolerance, plasma-free fatty acids, and plasma C Reactive Proteins. In conclusion, AG490 improved the inflammation and oxidative stress of neuronal, hepatic, and muscle tissues of stroke rats as well as impairing insulin signaling in the liver and skeletal muscles. Therefore, Jak2 blockades may have benefits for combating poststroke central and peripheral inflammation, and metabolic abnormalities.

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“… 115 In HIE, elevated inflammatory cytokine levels such as IL-6, TNF, and IL-8 recruit leukocytes to the site of injury and damage endothelial cell integrity. 116 , 117 In infants with HIE, early microvascular injury may have a critical impact on neuronal damage. 118 …”

Section: Endothelial Cells In Neonatal Disordersmentioning

confidence: 99%

Role of the Endothelium in Neonatal Diseases

Maheshwari¹,

Mezu‐Ndubuisi²

2022

Newborn

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In both fetal and neonatal physiologic and pathologic processes in most organs, endothelial cells are known to play critical roles. Although the endothelium is one of the most ubiquitous cell type in the body, the tight adherence to the blood vessel wall has made it difficult to study their diverse function and structure. In this article, we have reviewed endothelial cell origins and explored their heterogeneity in terms of structure, function, developmental changes, and their role in inflammatory and infectious diseases. We have also attempted to evaluate the untapped therapeutic potentials of endothelial cells in neonatal disease. This article comprises various peer-reviewed studies, including ours, and an extensive database literature search from EMBASE, PubMed, and Scopus.

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Angiopoietin 1 attenuates interleukin-6-induced endothelial cell permeability through SHP-1

Cited by 12 publications

References 25 publications

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

Jak2 Inhibitor AG490 Improved Poststroke Central and Peripheral Inflammation and Metabolic Abnormalities in a Rat Model of Ischemic Stroke

Role of the Endothelium in Neonatal Diseases

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