Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis

Chen, Shyi-Jou; Huang, Shing-Hwa; Chen, Jing-Wun; Wang, Kai-Chen; Yang, Yung-Rong; Liu, Pi-Fang; Lin, Gu‐Jiun; Sytwu, Huey‐Kang

doi:10.1016/j.intimp.2015.12.020

Cited by 69 publications

(54 citation statements)

References 47 publications

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“…Tissue protection afforded by melatonin is related to its double antioxidant actions, including: (1) Direct neutralization of devastative reactive oxygen and nitrogen species (ROS and RNS); and (2) Indirect effect through the activation of antioxidant enzymes—superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), or glutathione reductase (GR) [7,8,9,10]. In addition, melatonin modulates the inflammatory defense of the organism, decreasing the production of pro-inflammatory cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 22 (IL-22), tumor necrosis factor α (TNFα) and increasing the anti-inflammatory interleukin 10 (IL-10) [11,12,13,14,15,16]. Melatonin is able to control the above-mentioned processes at the cellular level via inhibition of NF-κB, a nuclear transcription factor responsible for the control of genes involved in cell apoptosis and the production of inflammatory mediators, whereas the activation of antioxidant enzymes by melatonin is possibly related to the stimulation of protein kinase C (PKC) and Ca 2+ influx via the induction and nuclear translocation of nuclear transcription factor Nrf1 [12,13,17].…”

Section: Melatonin Its Precursor and Derivativesmentioning

confidence: 99%

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

Jaworek

Leja-Szpak

Nawrot-Porąbka

et al. 2017

IJMS

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Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

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Section: Melatonin Its Precursor and Derivativesmentioning

confidence: 99%

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

Jaworek

Leja-Szpak

Nawrot-Porąbka

et al. 2017

IJMS

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“…As the biological roles of melatonin were widely studied, the recognized therapeutical effects and the health benefits of melatonin could cover a broad range. Melatonin could regulate human physiological rhythm, alleviate related disorders like jet lag [2] and insomnia [3], scavenge free radical species [4], enhance the immune system [5], show anti-aging [6] and anti-inflammatory effects [7] and perform anticancer activities [8]. Moreover, melatonin could also exhibit neuroprotective effects [9], facilitate the control of chronic diseases, such as cardiovascular diseases [10], diabetes [11] and obesity [12].…”

Section: Introductionmentioning

confidence: 99%

Dietary Sources and Bioactivities of Melatonin

et al. 2017

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Insomnia is a serious worldwide health threat, affecting nearly one third of the general population. Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. During the last decades, melatonin has been widely identified and qualified in various foods from fungi to animals and plants. Eggs and fish are higher melatonin-containing food groups in animal foods, whereas in plant foods, nuts are with the highest content of melatonin. Some kinds of mushrooms, cereals and germinated legumes or seeds are also good dietary sources of melatonin. It has been proved that the melatonin concentration in human serum could significantly increase after the consumption of melatonin containing food. Furthermore, studies show that melatonin exhibits many bioactivities, such as antioxidant activity, anti-inflammatory characteristics, boosting immunity, anticancer activity, cardiovascular protection, anti-diabetic, anti-obese, neuroprotective and anti-aging activity. This review summaries the dietary sources and bioactivities of melatonin, with special attention paid to the mechanisms of action.

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“…Another study, the only one on Lewis rats of 8‐12 weeks old, showed amelioration in melatonin‐treated EAE rats, through suppression of intercellular adhesion molecule‐1 (ICAM‐1) . Similarly, other researchers have used animals between 8 and 12 weeks old, without any comparison to animals at an earlier age. Importantly, an old study in the 1970s by Janković et al.…”

Section: Introductionmentioning

confidence: 99%

Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression

Ghareghani

Dokoohaki

Ghanbari

et al. 2016

Clin Exp Pharma Physio

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Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations.

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Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis

Cited by 69 publications

References 47 publications

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

Dietary Sources and Bioactivities of Melatonin

Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression

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