Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells

Caradonna, Fabio; Cruciata, Ilenia; Schifano, Ilaria; Rosa, Chiara La; Naselli, Flores; Chiarelli, Roberto; Perrone, Anna; Gentile, Carla

doi:10.1007/s00011-017-1124-5

Cited by 33 publications

(25 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, differentiated Caco‐2 cell monolayers represent a well‐characterized intestinal barrier model in vitro and have widely been used in bioavailability studies . On the other hand, differentiated Caco‐2 monolayers submitted to pro‐inflammatory action of LPS or cytokines have been proposed as in in vitro model of intestinal inflammation, which is useful for evaluating potential local effects of food, food components, or per oral drugs …”

Section: Resultsmentioning

confidence: 99%

“…Recently, we showed that proinflammatory actions of IL‐1β in differentiated Caco‐2 cells also involve epigenetic mechanisms. In particular, IL‐1β is able to change the methylation status acting as demethylating agent …”

Section: Resultsmentioning

confidence: 99%

“…27,28 On the other hand, differentiated Caco-2 monolayers submitted to pro-inflammatory action of LPS or cytokines have been proposed as in in vitro model of intestinal inflammation, which is useful for evaluating potential local effects of food, food components, or per oral drugs. 19,25,29 Melatonin, in addition to endogenous synthesis, may be sourced from dietary supplements and melatonin-rich foods. 30 These exogenous sources, furthermore to raising plasmatic concentration of melatonin, also increase its concentration in the lumen gut.…”

Section: Resultsmentioning

confidence: 99%

“…Isolation of genomic DNA from differentiated cells was carried out as previously reported . Methylation‐sensitive arbitrarily primed PCR (MeSAP‐PCR) was carried out on the differentiated Caco‐2 cells according to the literature …”

Section: Methodsmentioning

confidence: 99%

“…In particular, IL-1β is able to change the methylation status acting as demethylating agent. 25 Here, we investigated the effects of melatonin on the changes induced by IL-1β on DNA methylation (Figure 9). As expected, IL-1β-induced global DNA demethylation with respect to control cells but, surprisingly, also melatonin alone demethylated the DNA slightly.…”

Section: Dna Demethylationmentioning

confidence: 99%

See 4 more Smart Citations

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Dna Demethylationmentioning

confidence: 99%

See 3 more Smart Citations

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

show abstract

DNA demethylation of promoter region orchestrates SPI‐1‐induced ADAMTS‐5 expression in articular cartilage of osteoarthritis mice

Liu,

Lu,

et al. 2023

Journal Cellular Physiology

View full text Add to dashboard Cite

Osteoarthritis (OA) is one of the most prevalent joint diseases in aged people and characterized by articular cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Recent advances in OA research have clearly shown that OA development is associated with aberrant DNA methylation status of many OA‐related genes. As one of most important cartilage degrading proteases in OA, a disintegrin and metalloproteinase with thrombospondin motifs subtype 5 (ADAMTS‐5) is activated to mediate cartilage degradation in human OA and experimental murine OA models. The pathological factors and signaling pathways mediating ADAMTS‐5 activation during OA development are not well defined and have been a focus of intense research. ADAMTS‐5 promoter is featured by CpG islands. So far there have been no reports concerning the DNA methylation status in ADAMTS‐5 promoter during OA development. In this study, we sought to investigate DNA methylation status in ADAMTS‐5 promoter, the role of DNA methylation in ADAMTS‐5 activation in OA, and the underlying mechanisms. The potential for anti‐OA intervention therapy which is based on modulating DNA methylation is also explored. Our results showed that DNA methyltransferases 1 (Dnmt1) downregulation‐associated ADAMTS‐5 promoter demethylation played an important role in ADAMTS‐5 activation in OA, which facilitated SPI‐1 binding on ADAMTS‐5 promoter to activate ADAMTS‐5 expression. More importantly, OA pathological phenotype of mice was alleviated in response to Dnmt1‐induced DNA methylation of ADAMTS‐5 promoter. Our study will benefit not only for deeper insights into the functional role and regulation mechanisms of ADAMTS‐5 in OA, but also for the discovery of disease‐modifying OA drugs on the basis of ADAMTS‐5 via modulating DNA methylation status.

show abstract

Curcumin suppresses oxidative stress via regulation of ROS/NF-κB signaling pathway to protect retinal vascular endothelial cell in diabetic retinopathy

Huang

Qian

You

et al. 2021

Mol. Cell. Toxicol.

View full text Add to dashboard Cite

Background: Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus and a leading blindness disease in the world. The retinal vascular endothelial cells can be damaged by oxidative stress even in the early stage of diabetic retinopathy. NF-κB is a key transcription factor in cell apoptosis and oxidative stress. Curcumin can relieve oxidative stress induced by high glucose.This study aimed to investigate the effect of curcumin on the rat retinal vascular endothelial cells (RRVECs) in DR and to deduce the possible molecular mechanism.Methods: The cultured RRVECs were identified by both of vWF and CD31 expression.The RRVECs were divided into four groups: the normal control group, the osmolarity control group, the high glucose group and the curcumin treatment group (High glucose +Curcumin). We observed the different morphological changes in the groups by transmission electron microscopy. Oxidative stress was detected by flow cytometry. The Activation of ROS/NF-κB signal pathway was detected by electrophoretic Mobility Shift Assay (EMSA), immunohistochemistry and western-blot; the apoptosis of RRVECs was tested by flow cytometry.Results: We found that curcumin reduced the reactive oxygen species (ROS) and relieved the apoptosis in RRVECs exposed to the high glucose by flow cytometry. We detected that the increased activity of NF-κB and phosphorylated NF-κB in RRVECs induced by high glucose concentration was significantly suppressed by curcumin. Furthermore, based on the assay quantifying the level of apoptosis-related proteins, including bcl-2 and bax, we illustrated that curcumin could decrease the apoptosis of RRVECs induced by high glucose concentration. Conclusion:We concluded that ROS/NF-κB signaling pathway played an important role in the progress of DR and curcumin could suppress the oxidative stress via regulation of NF-κB signal to protect the RRVECs in DR. Background Diabetic retinopathy (DR) is one of the leading cause of blindness in working-age people in mainland China[1 2]. Pathophysiological studies have demonstrated that diabetic retinopathy brings about progressive changes of retinal microvasculature [3 4]. Typical early changes in the retinal vasculature 4 of diabetic eyes are pericyte loss, basement membrane thickening, the retinal vascular endothelial cell (RVEC) proliferation and blood-retina barrier leakage[5 6].Several studies [7][8][9][10] have shown that oxidative stress plays an important role in the pathogenesis of diabetic retinopathy. Oxidative stress activates multiple pathways in the cell, including signaling cascades, cell apoptosis, and transcription factors, which in turn cause the pathophysiological changes of the retinal vasculature in diabetic retinopathy. The RVECs are key participants in diabetic retinopathy. They not only supply oxygen and nutrients for the normal metabolism of the retina, but also contribute to the blood-retinal barrier that protects the retina [11 12]. NF-κB is a vital transcription factor that initiates the transcription of gen...

show abstract

Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells

Abstract: Our results suggest a potential role of IL-1β as modulator of DNA methylation in activated differentiated Caco-2 cell line.

Cited by 33 publications

References 40 publications

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

DNA demethylation of promoter region orchestrates SPI‐1‐induced ADAMTS‐5 expression in articular cartilage of osteoarthritis mice

Curcumin suppresses oxidative stress via regulation of ROS/NF-κB signaling pathway to protect retinal vascular endothelial cell in diabetic retinopathy

Contact Info

Product

Resources

About