Tie2 signalling through Erk1/2 regulates TLR4 driven inflammation

Smith, Tracy L.; Slyke, Paul Van; Jones, Nina; Dumont, Daniel; McGlade, C. Jane

doi:10.1016/j.cellsig.2018.08.001

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…The NF-κB signaling pathway plays a crucial role in regulating the expression of endothelial cell adhesion molecules such as E-selectin and VCAM-1 [24]. Several studies suggested that reduced Tie2 phosphorylation may lead to an increased expression of these adhesion molecules [11][12][13]25]. However, these studies did not report whether Tie2 was locally reduced in organs or whether reduced Tie2-phosphorylation levels coincided with changes in the cell adhesion molecule expression in particular microvascular segments in the organs.…”

Section: Discussionmentioning

confidence: 99%

Reduced Tie2 in Microvascular Endothelial Cells Is Associated with Organ-Specific Adhesion Molecule Expression in Murine Health and Endotoxemia

Zwiers

Lucas

Jongman

et al. 2023

Cells

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Endothelial cells (ECs) in the microvasculature in organs are active participants in the pathophysiology of sepsis. Tyrosine protein kinase receptor Tie2 (Tek; Tunica interna Endothelial cell Kinase) is thought to play a role in their inflammatory response, yet data are inconclusive. We investigated acute endotoxemia-induced changes in the expression of Tie2 and inflammation-associated endothelial adhesion molecules E-selectin and VCAM-1 (vascular cell adhesion molecule-1) in kidneys and lungs in inducible, EC-specific Tie2 knockout mice. The extent of Tie2 knockout in healthy mice differed between microvascular beds, with low to absent expression in arterioles in kidneys and in capillaries in lungs. In kidneys, Tie2 mRNA dropped more than 70% upon challenge with lipopolysaccharide (LPS) in both genotypes, with no change in protein. In renal arterioles, tamoxifen-induced Tie2 knockout was associated with higher VCAM-1 protein expression in healthy conditions. This did not increase further upon challenge of mice with LPS, in contrast to the increased expression occurring in control mice. Also, in lungs, Tie2 mRNA levels dropped within 4 h after LPS challenge in both genotypes, while Tie2 protein levels did not change. In alveolar capillaries, where tamoxifen-induced Tie2 knockout did not affect the basal expression of either adhesion molecule, a 4-fold higher E-selectin protein expression was observed after exposure to LPS compared to controls. The here-revealed heterogeneous effects of absence of Tie2 in ECs in kidney and lung microvasculature in health and in response to acute inflammatory activation calls for further in vivo investigations into the role of Tie2 in EC behavior.

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Section: Discussionmentioning

confidence: 99%

Reduced Tie2 in Microvascular Endothelial Cells Is Associated with Organ-Specific Adhesion Molecule Expression in Murine Health and Endotoxemia

Zwiers

Lucas

Jongman

et al. 2023

Cells

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“…In a previous study, Strasser et al (2016) found that tryptophan and phenylalanine were used in the body to synthesize serotonin, L-DOPA derivatives and 5, 6, 7, 8-tetrahydrobiopterin (BH4), which compounds can affect the severity of inflammation. In the study of Smith et al (2018) , tyrosine and phenylalanine participated in the regulation of TLR4 signaling pathways, thereby influencing the degree of inflammation. Phenylalanine also is part of the glycolytic and liposynthetic pathways ( Waisbren et al, 2007 ; Obianom et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Intramammary infusion of matrine-chitosan hydrogels for treating subclinical bovine mastitis —effects on milk microbiome and metabolites

Zhang

Wang²,

Ye³

et al. 2022

Front. Microbiol.

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BackgroundBovine metabolism undergoes significant changes during subclinical mastitis, but the relevant molecular mechanisms have not been elucidated. In this study we investigated the changes in milk microbiota and metabolites after intramammary infusion of matrine-chitosan hydrogels (MCHs) in cows with subclinical mastitis.MethodsInfusions were continued for 7 days, and milk samples were collected on days 1 and 7 for microbiome analysis by 16S rRNA gene sequencing and metabolite profiling by liquid chromatography-mass spectrometry.ResultsMCHs significantly decreased the somatic cell count on day 7 compared to day 1, and the Simpson index indicated that microbial diversity was significantly lower on day 7. The relative abundance of Aerococcus, Corynebacterium_1, Staphylococcus and Firmicutes was significantly decreased on day 7, while Proteobacteria increased. In the milk samples, we identified 74 differentially expressed metabolites. The MCHs infusion group had the most significantly upregulated metabolites including sphingolipids, glycerophospholipids, flavonoids and fatty acyls. The mammary gland metabolic pathways identified after MCHs treatment were consistent with the known antimicrobial and anti-inflammatory properties of matrine that are associated with glycerophospholipid metabolism and the sphingolipid metabolic signaling pathways.ConclusionThese insights into the immunoregulatory mechanisms and the corresponding biological responses to matrine demonstrate its potential activity in mitigating the harmful effects of bovine mastitis.

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“…Previous studies have proved that the MAPK pathway family, especially JNK, ERK1/2 and p38, regulate the inflammatory response and immune response (Ajizian, English, & Meals, 1999;Daniele et al, 2015;Smith et al, 2018). In recent years, the role of the NLRP3 inflammasome in immune regulation has received increasing attention (Chessa, Ganau, & Mazzarello, 2015).…”

Section: Discussionmentioning

confidence: 99%

Acrylamide induced the activation of NLRP3 inflammasome via ROS-MAPKs pathways in Kupffer cells

Nan

Yuan

Yan

et al. 2019

Food and Agricultural Immunology

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Acrylamide (AA) is an important product of the Maillard reaction. Studies have demonstrated that AA caused oxidative stress damage in liver, which in turn triggered an inflammatory response, and the activation of NOD-like receptor protein-3 (NLRP3) inflammasome played a key factor in regulating inflammation. Therefore, we hypothesized NLRP3 inflammasome activation was involved in AAinduced inflammatory response. AA induced the reactive oxygen species (ROS) overproduction, accompanied by the MAPK pathway activation, which resulted in NLRP3 inflammasome formation, and eventually increased IL-1β and IL-18 release. The activation of the MAPK pathway was inhibited when using ROS scavenger (NAC). And when MAPK selective inhibitors were used, KCs viability was increased though AA-treated. Meanwhile the NLRP3 inflammasome activation was inhibited, which decreased the release of the cellular inflammatory secretion factors IL-1β and IL-18. Overall, the activation of ROS-MAPK-NLRP3-IL-1β signalling axis induced by AA plays an important role in the process of inflammation.Signaling pathways involved in inflammation induced by AA. After AA stimulated KCs, a large amount of ROS were released. ROS activated MAPK signaling pathway to promote the activation of NLRP3 inflammasome. Activation of NLRP3 signaling activated Caspase-1, resulting in the maturation of IL-1β and IL-18. The activation of NLRP3 inflammasome was inhibited and the levels of cytoinflammatory factor IL-1β and IL-18 were decreased when using MAPK selective inhibitors.

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Tie2 signalling through Erk1/2 regulates TLR4 driven inflammation

Cited by 5 publications

References 44 publications

Reduced Tie2 in Microvascular Endothelial Cells Is Associated with Organ-Specific Adhesion Molecule Expression in Murine Health and Endotoxemia

Reduced Tie2 in Microvascular Endothelial Cells Is Associated with Organ-Specific Adhesion Molecule Expression in Murine Health and Endotoxemia

Intramammary infusion of matrine-chitosan hydrogels for treating subclinical bovine mastitis —effects on milk microbiome and metabolites

Acrylamide induced the activation of NLRP3 inflammasome via ROS-MAPKs pathways in Kupffer cells

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