DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation

Wang, Xinxuan; Feng, Zhihui; Li, Qimeng; Yi, Benshun; Xu, Qiong

doi:10.1007/s00441-018-2826-x

Cited by 22 publications

(20 citation statements)

References 42 publications

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“…These dynamic changes in TET family enzyme expression during the conditioning period led us to further study their involvement in the creation of EHC-induced cross-tolerance to inflammation. Interestingly, TET family enzymes have been previously reported to regulate different inflammatory events: e.g., activating inflammatory genes during macrophage differentiation and monocyte activation in monogenic inflammatory syndromes (Vento-Tormo et al, 2017); resolving inflammation in human peripheral blood mononuclear cells and murine peritoneal macrophages (Zhang et al, 2015); inducing cytokine expression in human dental pulp cells (Wang et al, 2018); and exhibiting TET-dependent anti-inflammatory cytokine regulation in human PMA-differentiated THP-1 cells and human primary mononuclear cells (Hassan et al, 2018), and adaptive immunity in zebrafish (Yang et al, 2016). However, little is known about the TET family enzymes' role in regulating CNS inflammation.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…These results indicate that 5-Aza-CdR accelerates the inflammatory process by the activation of TRAF6 [ 107 ]. Besides, TET2 improves the inflammatory response in the DPSCs by regulating the levels of 5hmC on the MyD88 promoter [ 108 ].…”

Section: Epigenetic Mechanisms In Dpscsmentioning

confidence: 99%

Epigenetic Regulation of Dental Pulp Stem Cell Fate

Zhou

Gan

Yan

et al. 2020

Stem Cells International

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Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

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“…Tet1 and Tet2 then enhanced the Foxp3 promoter hypomethylation, which promoted Treg differentiation to further regulate the autoimmune response [21]. TET2 participates in the LPS-induced inflammatory response in human dental pulp cells by epigenetically regulating the transcription of the NF-κB signaling pathway transduction molecule MyD88 [22]. Thus, TET proteins can impact the expression of particular genes and change the process of inflammation by different mechanisms.…”

Section: Introductionmentioning

confidence: 99%

TET1 Knockdown Inhibits Porphyromonas gingivalis LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells

Huang

Tian

et al. 2019

IJMS

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Tet-eleven translocation 1 (TET1) is a dioxygenase that plays an important role in decreasing the abundance of DNA methylation and changing the expression levels of specific genes related to inflammation. Porphyromonas gingivalis (Pg.) lipopolysaccharide (LPS) can induce periodontal diseases that present with severe bone loss and collagen fiber destruction accompanied by a high number of M1 macrophages. M1-polarized macrophages are pivotal immune cells that promote the progression of the periodontal inflammatory response, but the function of TET1 during M1 macrophage activation is still unknown. Our results showed that the mRNA and protein expression levels of TET1 decreased in THP-1 cells during M1 macrophage differentiation. TET1 knockdown resulted in a significant decrease in the production of proinflammatory markers such as IL-6, TNF-α, CCL2, and HLA-DR in Pg. LPS/IFN-γ- and Escherichia coli (E. coli) LPS/IFN-γ-induced M1 macrophages. Mechanistically, TET1 knockdown downregulated the activity of the NF-κB signaling pathway. After treatment with the NF-κB inhibitor BAY 11-7082, M1 marker expression showed no significant difference between the TET1 knockdown group and the control group. Taken together, these results suggest that TET1 depletion inhibited Pg. LPS/IFN-γ-induced M1 macrophage polarization through the NF-κB pathway in THP-1 cells.

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DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation

Cited by 22 publications

References 42 publications

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

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

Epigenetic Regulation of Dental Pulp Stem Cell Fate

TET1 Knockdown Inhibits Porphyromonas gingivalis LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells

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