TET-2 up-regulation is associated with the anti-inflammatory action of Vicenin-2

Hassan, N. M.; Ali, Ahmed; Withycombe, Cathryn; Ahluwalia, Maninder; Al-Nasseri, Raya Hamdan; Tonks, Alex; Morris, Keith

doi:10.1016/j.cyto.2018.03.016

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…The TET2 activating effects of vitamin C have been validated in multiple cell types and in vivo (Agathocleous, et al, 2017;Cimmino, et al, 2017;. More recently, another potential TET2 activator from natural sources, vicenin-2, has been identified to ameliorate high glucose induced endothelial inflammation (including hyperpermeability, leukocyte adhesion, ROS production, and NF-kB dependent adhesion molecules expression) (Ku & Bae, 2016), as well as LPS induced macrophage inflammation (TNFα, IL1β, and IL18) (Hassan, et al, 2018), underscoring the potential of TET2 activators to prevent atherosclerosis development. Further studies are necessary to validate, whether TET2 activation directly contribute to these compounds-mediated atheroprotection.…”

Section: Tet2 Activatorsmentioning

confidence: 99%

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Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Kamato

Little

et al. 2019

Pharmacology & Therapeutics

112

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Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms. The epigenetic basis of atherosclerosis has transformed our knowledge of epigenetics from an important biological phenomenon to a burgeoning field of cardiovascular research. Here, we provide a systematic and up-to-date overview of the current knowledge of three distinct but interrelated epigenetic processes (including DNA methylation, histone methylation/acetylation, and noncoding RNAs), in atherosclerotic plaque development and instability. Mechanistic and conceptual advances in understanding the biological roles of various epigenetic modifiers in regulating gene expression and functions of endothelial cells (vascular homeostasis, leukocyte adhesion, endothelial-mesenchymal transition, angiogenesis, and mechanotransduction), smooth muscle

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Section: Tet2 Activatorsmentioning

confidence: 99%

“…Gender is an important determinant of the incidence of CVD. A recent study (Hassan, et al, 2018) has shown that estrogen can promote phosphorylation-dependent EZH2 degradation via PI3K/Akt pathway, suggesting that sex hormone-dependent modulation of chromatin modifiers could be partially responsible for sex dimorphism.…”

mentioning

confidence: 99%

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Kamato

Little

et al. 2019

Pharmacology & Therapeutics

112

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“…TET family enzymes have been reported to regulate different types of inflammation (Yang et al, 2016;Vento-Tormo et al, 2017;Hassan et al, 2018), as well as contribute to macrophage polarization and activation (Wallner et al, 2016). Although changes in DNA methylation during CNS inflammation have been previously reported (Ligthart et al, 2016), little is known about the role of TET family enzymes during CNS inflammation.…”

Section: Introductionmentioning

confidence: 99%

Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life

et al. 2020

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Early life encounters with stress can lead to long-lasting beneficial alterations in the response to various stressors, known as cross-tolerance. Embryonic heat conditioning (EHC) of chicks was previously shown to mediate resilience to heat stress later in life. Here we demonstrate that EHC can induce cross-tolerance with the immune system, attenuating hypothalamic inflammation. Inflammation in EHC chicks was manifested, following lipopolysaccharide (LPS) challenge on day 10 post-hatch, by reduced febrile response and reduced expression of LITAF and NFκB compared to controls, as well as nuclear localization and activation of NFκB in the hypothalamus. Since the crosstolerance effect was long-lasting, we assumed that epigenetic mechanisms are involved. We focused on the role of ten-eleven translocation (TET) family enzymes, which are the mediators of active CpG demethylation. Here, TET transcription during early life stress was found to be necessary for stress resilience later in life. The expression of the TET family enzymes in the midbrain during conditioning increased in parallel to an elevation in concentration of their cofactor α-ketoglutarate. In-ovo inhibition of TET activity during EHC, by the α-ketoglutarate inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES), resulted in reduced total and locus specific CpG demethylation in 10-day-old chicks and reversed both thermal and inflammatory resilience. In addition, EHC attenuated the elevation in expression of the stress markers HSP70, CRHR1, and CRHR2, during heat challenge on day 10 post-hatch. This reduction in expression was reversed by BPTES. Similarly, the EHC-dependent reduction of inflammatory gene expression during LPS challenge was eliminated in BPTES-treated chicks. Thus, TET family enzymes and CpG demethylation are essential for the embryonic induction of stress cross-tolerance in the hypothalamus.

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“…The importance of mutations such as TET-2 in the pathogenesis of atherosclerosis was reported recently by Jaiswal et al [27,28] and its potential importance as a novel target in atherosclerosis. In their study Hassan et al [20] proposed the anti-inflammatory actions of another naturally occurring glycosidic flavonoid vicenin-2 (V2) in phorbol myristate acetate (PMA)-differentiated THP-1 cells (dTHP-1) and that its anti-inflammatory actions where associated with upregulating of TET-2. This study supports the hypothesis that the anti-inflammatory properties of other naturally occurring compounds can be associated with the upregulation of TET-2 in endothelia cells.…”

Section: A B Cmentioning

confidence: 99%

“…We have recently demonstrated that a naturally occurring glycosidic flavonoid, Vicenin-2 could regulate Lipopolysaccharide (LPS) reduced inflammatory cytokine secretion significantly increased TET-2 expression and NLRP3 expression in human macrophages [20]. Given the importance of endothelial cells in the regulation of arterial inflammation, we hypothesised that an extract of Nigella seeds and its major component TQ, could regulate inflammatory cytokine secretion and monocyte chemoattractant regulators in an immortalised human endothelial cell model.…”

Section: Introductionmentioning

confidence: 99%

Nigella sativa Extract and Thymoquinone Regulate Inflammatory Cytokine and TET-2 Expression in Endothelial Cells

Amartey¹,

Gapper²,

Hussein³

et al. 2019

Artery Res

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Numerous natural compounds including Nigella sativa (N. sativa) demonstrate anti-inflammatory and anti-diabetic antiangiogenic properties. Lipopolysaccharide (LPS) mediated inflammation is regarded as an important contributor to the inflammation that is associated with the development of arteriosclerosis. In this study, it was hypothesised that N. sativa Extract (NSE) and its main active component Thymoquinone (TQ) could potentially inhibit LPS mediated inflammatory cytokine secretion and monocyte recruitment factors and monocyte in Human Vascular Endothelial Cell (HECV) lines. In addition the Ten-Eleven Translocation (TET-2) an epigenetic regulator, increasingly regarded has having a major role in both the regulation of cytokine secretion and in the development of atherosclerosis through its ability to inhibit the inflammasome Nod-like Receptor Protein 3 (NLRP3) and Interleukin-1b (IL-1b) secretion was investigated. NSE significantly inhibited the production of both IL-6 and-8 and both NSE and TQ inhibited the gene expression of vascular endothelial growth factor and monocyte chemotactic protein-1 in HECV cells. NSE and TQ inhibited the gene expression of NLRP3 and IL-1b and significantly upregulated the gene expression of TET-2 in the presence of LPS. To conclude, NSE and TQ attenuated inflammatory and monocyte recruitment response and also demonstrate a potentially important role in regulating both NLRP3 and TET-2 expression.

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TET-2 up-regulation is associated with the anti-inflammatory action of Vicenin-2

Cited by 16 publications

References 22 publications

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life

Nigella sativa Extract and Thymoquinone Regulate Inflammatory Cytokine and TET-2 Expression in Endothelial Cells

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