Platelet-activating factor and hydrogen peroxide exert a dual modulatory effect on the transcription of LXRα and its target genes in human neutrophils

Reyes-Quiróz, María Edith; Álba, Gonzalo; Sáenz, Javier; Geniz, Isabel; Jiménez, Juan; Martı́n-Nieto, José; Santa-María, Consuelo; Sobrino, Francisco

doi:10.1016/j.intimp.2016.05.001

Cited by 4 publications

(5 citation statements)

References 47 publications

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“…The controversial results may indicate that ROS regulation of NF-κB activity at inflammatory sites is more complex than previously thought and that ROS may exert both, pro- and anti-inflammatory effects. While low doses of H 2 O 2 seem to trigger NF-κB activation, high oxidative stress does not alter or even adversely affect the NF-κB status (388, 389). Comparably, myeloperoxidase was recently reported to engage in a negative feedback loop of NF-κB downregulation to dampen the pro-inflammatory cytokine response (390).…”

Section: Neutrophilsmentioning

confidence: 99%

Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis

et al. 2019

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The transcription factor NF-κB is a central mediator of inflammation with multiple links to thrombotic processes. In this review, we focus on the role of NF-κB signaling in cell types within the vasculature and the circulation that are involved in thrombo-inflammatory processes. All these cells express NF-κB, which mediates important functions in cellular interactions, cell survival and differentiation, as well as expression of cytokines, chemokines, and coagulation factors. Even platelets, as anucleated cells, contain NF-κB family members and their corresponding signaling molecules, which are involved in platelet activation, as well as secondary feedback circuits. The response of endothelial cells to inflammation and NF-κB activation is characterized by the induction of adhesion molecules promoting binding and transmigration of leukocytes, while simultaneously increasing their thrombogenic potential. Paracrine signaling from endothelial cells activates NF-κB in vascular smooth muscle cells and causes a phenotypic switch to a “synthetic” state associated with a decrease in contractile proteins. Monocytes react to inflammatory situations with enforced expression of tissue factor and after differentiation to macrophages with altered polarization. Neutrophils respond with an extension of their life span—and upon full activation they can expel their DNA thereby forming so-called neutrophil extracellular traps (NETs), which exert antibacterial functions, but also induce a strong coagulatory response. This may cause formation of microthrombi that are important for the immobilization of pathogens, a process designated as immunothrombosis. However, deregulation of the complex cellular links between inflammation and thrombosis by unrestrained NET formation or the loss of the endothelial layer due to mechanical rupture or erosion can result in rapid activation and aggregation of platelets and the manifestation of thrombo-inflammatory diseases. Sepsis is an important example of such a disorder caused by a dysregulated host response to infection finally leading to severe coagulopathies. NF-κB is critically involved in these pathophysiological processes as it induces both inflammatory and thrombotic responses.

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Section: Neutrophilsmentioning

confidence: 99%

Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis

et al. 2019

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“…(22) Hydrogen peroxide is widely implicated by both inducing PAF synthesis and being intracellularly produced by PAF in immune cells. (23) Accordingly, using the PAF-R antagonist, WEB2086, in our WST-8 assay was effective in improving the cell viability with EP stimulation. These data demonstrate that PAF-R can be a potential source of intracellular ROS production, particularly intracellular hydrogen peroxide, in this system.…”

Section: Discussionmentioning

confidence: 91%

“…HaCaT keratinocytes express functional PAF-Rs and synthesize the potent inflammatory lipid mediator, PAF.‍ ( 20 , 21 ) PAF and other PAF-R agonists are produced in response to UVRs, and ultimately cause an increase in intracellular ROS levels.‍ ( 22 ) Hydrogen peroxide is widely implicated by both inducing PAF synthesis and being intracellularly produced by PAF in immune cells.‍ ( 23 ) Accordingly, using the PAF-R antagonist, WEB2086, in our WST-8 assay was effective in improving the cell viability with EP stimulation. These data demonstrate that PAF-R can be a potential source of intracellular ROS production, particularly intracellular hydrogen peroxide, in this system.…”

Section: Discussionmentioning

confidence: 99%

Singlet oxygen from endoperoxide initiates an intracellular reactive oxygen species release in HaCaT keratinocytes

Elshafei

Minamiyama

2022

J. Clin. Biochem. Nutr.

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Singlet oxygen ( 1 O 2 ) is a selective intermediate reactive oxygen species generated naturally in biological systems by light-and non-light mediated processes. Although 1 O 2 plays an important role in cell signaling and in maintaining homeostasis, it can be toxic due to its ability to diffuse across considerable distances. Several in vitro studies have investigated the pathways by which 1 O 2 mediates oxidation of biological molecules and potential pathogenesis. However, understanding how singlet oxygen exerts cell injury through the production of subsequent reactive oxygen species remains unexplored. To study this, we used a hydrophobic endoperoxide as a source of 1 O 2 . Endoperoxides are reagents that quantitatively generate singlet oxygen in solution at 35°C by thermal decomposition. Our chemiluminescence and cell viability assay data revealed that 1 O 2 stimulated a secondary intracellular reactive oxygen species production in a very short time. To determine the source of these reactive oxygen species with endoperoxide exposure, cells were treated with inhibitors targeting NADPH oxidases and platelet activating factor receptors. Our results showed that addition of the platelet activating factor receptor antagonist, Apafant (WEB2086), alleviated cell injury and hydrogen peroxide levels following endoperoxide stimulation. Furthermore, intracellular calcium assay data demonstrated a potential calcium sensitive production of intracellular reactive oxygen species.

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“…12,40 In this article we detected that a pro-oxidant stimuli, naringenin, induced a clear LXRα and target genes stimulation, this effect had been previously detected by us in neutrophils with other strong prooxidant agents at high concentrations, platelet-activating factor (PAF) and H 2 O 2 . 41 We concluded that a low ROS production inhibited LXRα expression but high ROS production induced LXRα and target genes mRNA expression. This was confirmed with a previous treatment with NAC, a known antioxidant molecule that reduced naringenin-induced LXRα and target genes mRNA expression in human macrophages THP-1.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 85%

“…We have reported previously that he status redox cellular is essential for the activity LXRα. Pro-oxidant molecules inhibit LXRα production and antioxidant compound reverted this effect and even enhanced LXRα expression. , In this article we detected that a pro-oxidant stimuli, naringenin, induced a clear LXRα and target genes stimulation, this effect had been previously detected by us in neutrophils with other strong pro-oxidant agents at high concentrations, platelet-activating factor (PAF) and H 2 O 2 . We concluded that a low ROS production inhibited LXRα expression but high ROS production induced LXRα and target genes mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Grapefruit Flavonoid Naringenin Regulates the Expression of LXRα in THP-1 Macrophages by Modulating AMP-Activated Protein Kinase

et al. 2017

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The present work investigates the modulation of grapefruit flavonoid naringenin over liver X receptor alpha (LXRα) and its target genes in THP-1 macrophages, focusing on AMP-activated protein kinase (AMPK) implication. Naringenin induced LXRα at mRNA and protein levels besides influencing the expression of LXRα target genes ABCA1, ABCG1 (ATP-binding cassette A1 and G1), and SREBP1c (sterol response element binding protein 1c) in THP-1 macrophages. The increased LXRα mRNA and protein expression was reverted when AMPK was inhibited by its chemical inhibitor, compound C or by transfection with AMPK α1 and α2 siRNA. Naringenin treatments were also able to promote reverse cholesterol transport in THP-1 cells, which is in line with the increase in the ABCA1 and ABCG1 expression found. Treatments with this flavonoid also inhibited cell migration in THP-1 cells. In conclusion, LXRα and its target genes are up-regulated by naringenin in an AMPK dependent manner in human macrophages. The enhancement in the expression of genes involved in cholesterol efflux may reveal a new mechanism by which this polyphenol can prevent atherosclerosis and foam cell progression.

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Platelet-activating factor and hydrogen peroxide exert a dual modulatory effect on the transcription of LXRα and its target genes in human neutrophils

Cited by 4 publications

References 47 publications

Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis

Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis

Singlet oxygen from endoperoxide initiates an intracellular reactive oxygen species release in HaCaT keratinocytes

Grapefruit Flavonoid Naringenin Regulates the Expression of LXRα in THP-1 Macrophages by Modulating AMP-Activated Protein Kinase

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