Regulation of the Interleukin-6 gene expression during monocytic differentiation of HL-60 cells by chromatin remodeling and methylation

Poplutz, Magdalena K.; Weßels, Inga; Rink, Lothar; Uciechowski, Peter

doi:10.1016/j.imbio.2014.03.016

Cited by 50 publications

(37 citation statements)

References 28 publications

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“…Dandrea et al [26] reported that the repression of IL-6 is mediated by the binding of methyl-CpG-binding protein 2 (MeCP2) and histone 3 methylated on lysine 9 to the methylated CpG sites in pancreatic adenocarcinoma cell lines. Similar results were observed by Poplutz et al [25]. …”

Section: Discussionsupporting

confidence: 92%

“…Several studies showed that methylation of distinct CpG sites within the IL-6 promoter region correlates with mRNA expression [25,26,36]. This may imply a mechanistic link between promoter methylation and regulation of mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…1). However, studies have shown that the CpG methylation of this region influences the remodeling of chromatin and, consequently, the accessibility of chromatin for transcription factors [25,26]. Dandrea et al [26] reported that the repression of IL-6 is mediated by the binding of methyl-CpG-binding protein 2 (MeCP2) and histone 3 methylated on lysine 9 to the methylated CpG sites in pancreatic adenocarcinoma cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…1). However, these CpG sites were described to be involved in the remodeling of chromatin and, consequently, to alter the accessibility for transcription factors [25,26]. …”

Section: Introductionmentioning

confidence: 99%

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Interleukin-6 CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls

et al. 2015

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Background/Aims: Diabetes mellitus type 2 (DMT2) is accompanied by systemic low-grade inflammation with elevated levels of interleukin-6 (IL-6), which is encoded by a gene (IL-6) previously shown to be regulated by DNA methylation. We investigated seven CpG sites in IL-6 in individuals with DMT2, obese individuals and lean controls. Further, the DMT2 group received the glucagon-like peptide 1 agonist liraglutide. Methods: Blood samples were taken at the beginning of the study and after 4 months. The DNA methylation was assessed using pyrosequencing. Results: Methylation levels at the CpG sites -664, -628 and +13 at the first sampling time point (T1) and at -666 and -664 at the second sampling time point (T2) correlated negatively with initial body weight in the DMT2 group. We found positive correlations for the obese and the lean control group. In the obese group, CpG +27 methylation at T1 correlated with initial body weight (r = 0.685; p = 0.014). In the lean group, CpG -664 at T1 (r = 0.874; p = 0.005) and CpG -628 at T2 (r = 0.632; p = 0.050) correlated with initial body weight. Conclusion: These findings are an informative basis for further studies to elucidate epigenetic mechanisms underlying DMT2. Additionally, our results might provide starting points for the development of biomarkers for prevention and therapy strategies.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…1). However, these CpG sites were described to be involved in the remodeling of chromatin and, consequently, to alter the accessibility for transcription factors [25,26]. …”

Section: Introductionmentioning

confidence: 99%

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Interleukin-6 CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls

et al. 2015

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“…Promoter methylation is one of the regulation mechanisms of IL-6 gene expression and is correlated to body weight [51,81]. Furthermore, studies revealed an association between elevated mRNA levels of interleukin 6 and a Promoter demethylation [82,83]. IL-6 expression is modulated by the nuclear factor kappa B (NF-KB) whose activation was shown to be blocked by EGCG via inhibition of I kappa B kinase activity in the intestinal epithelial cell line IEC-6 [84].…”

Section: Discussionmentioning

confidence: 99%

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Pointner¹,

Magnet²,

Tomeva³

et al. 2017

J Nutr Food Sci

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Objective: In vitro and in vivo studies in rodents have demonstrated many health promoting properties of individual phytochemicals including antioxidative and chemopreventive effects. Recently combination of substances is claimed to enhance activity.The objective of this study was to investigate health benefits of a daily consumption of a combination of a large variety of phytochemicals (TimeBlock ® ). To assess potential changes we analyzed specific biomarkers that are associated with aging, oxidative stress and DNA stability: Methylation of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Methods:For this study 110 healthy participants of both sexes between 31-76 years were recruited, 101 subjects were included in further analysis. A small reference group (n=20) without intervention within the same age interval served as control. Participants received a plant based dietary supplement (TimeBlock ® ) for 6 months by oral administration. Ingredients included extracts from green tea (EGCG), wheatgrass (tocotrienols), barley grass (folic acid), tomatoes (lycopene), tagetes (zeaxanthin, lutein), algae, shiitake mushrooms (vitamin D) and grape seeds (resveratrol). Capillary blood samples were collected from all participants before administration and within 6 days after the end of the study period following DNA extraction, bisulfite conversion and qPCR as well as high resolution melting curve analysis addressing analysis of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Nutrition, lifestyle and health status were assessed with a standardized food and lifestyle questionnaire. Results and discussion:Our results confirmed the positive effect of plant derived antioxidants on telomeres and inflammation frequency. An age-specific drift of analyzed markers could be observed. While methylation of c-Myc-a key factor in telomerase regulation-was not affected by administration, total telomere length showed a significant increase, which we suggest to be linked with an increased cell turnover and accelerated apoptosis of senescent or mutated cells without enhancing telomerase activity. Further, methylation of mismatch repair protein gene MLH1 showed a strong negative correlation with telomere length, supporting the influence of MMR on telomere regulation. Conclusion:The results of the present study indicate that a combined administration of a variety of phytochemicals can be a potential preventive and therapeutic agent, as each substance exhibits different modes of action and in combination, health promoting effects could be potentiated. Addressing different mechanisms of aging, specific phytochemicals could be used as new therapeutic approach against age-related diseases.

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The intrinsic microglial clock system regulates interleukin‐6 expression

Nakazato

Hotta

Yamada

et al. 2016

Glia

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Similar to neurons, microglia have an intrinsic molecular clock. The master clock oscillator Bmal1 modulates interleukin-6 upregulation in microglial cells exposed to lipopolysaccharide. Bmal1 can play a role in microglial inflammatory responses. We previously demonstrated that gliotransmitter ATP induces transient expression of the clock gene Period1 via P2X7 purinergic receptors in cultured microglia. In this study, we further investigated mechanisms underlying the regulation of pro-inflammatory cytokine production by clock molecules in microglial cells. Several clock gene transcripts exhibited oscillatory diurnal rhythmicity in microglial BV-2 cells. Real-time luciferase monitoring also showed diurnal oscillatory luciferase activity in cultured microglia from Per1::Luciferase transgenic mice. Lipopolysaccharide (LPS) strongly induced the expression of pro-inflammatory cytokines in BV-2 cells, whereas an siRNA targeting Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), a core positive component of the microglial molecular clock, selectively inhibited LPS-induced interleukin-6 (IL-6) expression. In addition, LPS-induced IL-6 expression was attenuated in microglia from Bmal1-deficient mice. This phenotype was recapitulated by pharmacological disruption of oscillatory diurnal rhythmicity using the synthetic Rev-Erb agonist SR9011. Promoter analysis of the Il6 gene revealed that Bmal1 is required for LPS-induced IL-6 expression in microglia. Mice conditionally Bmal1 deficient in cells expressing CD11b, including microglia, exhibited less potent upregulation of Il6 expression following middle cerebral artery occlusion compared with that in control mice, with a significant attenuation of neuronal damage. These results suggest that the intrinsic microglial clock modulates the inflammatory response, including the positive regulation of IL-6 expression in a particular pathological situation in the brain, GLIA 2016. GLIA 2017;65:198-208.

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Regulation of the Interleukin-6 gene expression during monocytic differentiation of HL-60 cells by chromatin remodeling and methylation

Cited by 50 publications

References 28 publications

<b><i>Interleukin-6</i></b> CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls

<b><i>Interleukin-6</i></b> CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

The intrinsic microglial clock system regulates interleukin‐6 expression

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