Melatonin suppresses nitric oxide production in glial cultures by pro-inflammatory cytokines through p38 MAPK inhibition

Vilar-Bergua, Andrea; Lemos, Luisa de; Patraca, Iván; Martínez, Nohora; Folch, Jaume; Junyent, Fèlix; Verdaguer, Ester; Pallàs, Mercè; Auladell, Carme; Camins, Antoni

doi:10.3109/10715762.2013.845295

Cited by 26 publications

(19 citation statements)

References 41 publications

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“…Moreover, several studies showed inhibition of iNOS expression by melatonin in various cell types. [41][42][43] Our results indicate that melatonin protects against the nitrooxidative damage on IECs and suggest that this protection may involve not only the known scavenging activity of melatonin against peroxynitrite 44 but also its ability to reduce NO release.…”

Section: Melatonin Inhibits Induced No Release From Stimulated Cacomentioning

confidence: 61%

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

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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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.

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Section: Melatonin Inhibits Induced No Release From Stimulated Cacomentioning

confidence: 61%

“…Although the NO scavenging activity of melatonin is known, the effects of melatonin on the levels of nitrite in the cell medium of stimulated Caco‐2 cells should be the consequence of iNOS downregulation. Moreover, several studies showed inhibition of iNOS expression by melatonin in various cell types …”

Section: Resultsmentioning

confidence: 99%

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

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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“…Melatonin suppressed MUC5AC production via the inhibition of Erk phosphorylation in EGF‐stimulated H292 cells. Additionally, the suppressive effects of melatonin on MAPKs phosphorylation have been previously described in many other reports . Based on these evidences, the pharmacological effects of melatonin involve the inhibition of MAPKs phosphorylation and melatonin is considered to have therapeutic potential for MAPKs‐related inflammatory pulmonary diseases, such as chronic bronchitis and pneumonitis induced by bacteria.…”

Section: Discussionmentioning

confidence: 80%

Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke‐induced chronic obstructive pulmonary diseases via the suppression of Erk‐Sp1 signaling

Shin

Park

et al. 2014

Journal of Pineal Research

103

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The incidence of chronic obstructive pulmonary disease (COPD) has substantially increased in recent decade. Cigarette smoke (CS) is the most important risk factor in the development of COPD. In this study, we investigated the effects of melatonin on the development of COPD using a CS and lipopolysaccharide (LPS)-induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell. On day 4, the mice were treated intranasally with LPS. The mice were exposed to CS for 1 hr per day (8 cigarettes per day) from day 1 to day 7. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 hr before CS exposure. Melatonin markedly decreased the neutrophil count in the BALF, with reduction in the proinflammatory mediators and MUC5AC. Melatonin inhibited Erk phosphorylation and Sp1 expression induced by CS and LPS treatment. Additionally, melatonin decreased airway inflammation with a reduction in myeloperoxidase expression in lung tissue. In in vitro experiments, melatonin suppressed the elevated expression of proinflammatory mediators induced by CSC treatment. Melatonin reduced Erk phosphorylation and Sp1 expression in CSC-stimulated H292 cells. In addition, cotreatment of melatonin and Erk inhibitors significantly limited the proinflammatory mediators with greater reductions in Erk phosphorylation and Sp1 expression than that observed in H292 cells treated with Erk inhibitor alone. Taken together, melatonin effectively inhibited the neutrophil airway inflammation induced by CS and LPS treatment, which was closely related to downregulation of Erk phosphorylation. These findings suggest that melatonin has a therapeutic potential for the treatment of COPD.

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“…Moreover, NO levels were linked to neural precursor cell (NPC) survival and cell fate determination [49], that is, elevated levels of NO suppress NSC proliferation and enhance differentiation of NPCs into astrocytes [50, 51]. Melatonin is a hormone synthesized in the pineal gland [52] with indirect antioxidant abilities through induction of antioxidant enzymes [53] and inhibiting NO production in glial cultures through p38 inhibition [54]. It has been shown to protect NSCs against lipopolysaccharide- (LPS-) induced inflammation [52].…”

Section: Neural Stem Cells (Nscs)mentioning

confidence: 99%

Effects of Antioxidant Supplements on the Survival and Differentiation of Stem Cells

Shaban

El-Husseny

Abushouk

et al. 2017

Oxidative Medicine and Cellular Longevity

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Although physiological levels of reactive oxygen species (ROS) are required to maintain the self-renewal capacity of stem cells, elevated ROS levels can induce chromosomal aberrations, mitochondrial DNA damage, and defective stem cell differentiation. Over the past decade, several studies have shown that antioxidants can not only mitigate oxidative stress and improve stem cell survival but also affect the potency and differentiation of these cells. Further beneficial effects of antioxidants include increasing genomic stability, improving the adhesion of stem cells to culture media, and enabling researchers to manipulate stem cell proliferation by using different doses of antioxidants. These findings can have several clinical implications, such as improving neurogenesis in patients with stroke and neurodegenerative diseases, as well as improving the regeneration of infarcted myocardial tissue and the banking of spermatogonial stem cells. This article reviews the cellular and molecular effects of antioxidant supplementation to cultured or transplanted stem cells and draws up recommendations for further research in this area.

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Melatonin suppresses nitric oxide production in glial cultures by pro-inflammatory cytokines through p38 MAPK inhibition

Cited by 26 publications

References 41 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

Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke‐induced chronic obstructive pulmonary diseases via the suppression of Erk‐Sp1 signaling

Effects of Antioxidant Supplements on the Survival and Differentiation of Stem Cells

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