Melatonin enhances lymphocyte proliferation and decreases the release of pituitary pro-opiomelanocortin-derived peptides in surgically traumatized rats

399

343

: Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age‐ and disease‐associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase‐reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross‐connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue‐specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.

Section: Position Of Melatonin In Synchronizer Cascadesmentioning

confidence: 99%

Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling

Hardeland

Madrid

Tan

et al. 2011

399

343

“…These studies indicate that melatonin stimulates cell proliferation of avian astrocytes [21], dentate neurons [22,23], epididymal epithelial cells [24], lymphocytes [25,26], mesenchymal stem cells [27], as well as increases cell survival of hippocampal neurons [28]. Pharmacological studies also reported that melatonin exerts its proliferative function on different cell types following a variety of experimental insults [29][30][31][32]. It is suggested that the proliferative effects of melatonin are largely mediated through the receptor-dependent signaling pathway [31,33,34].…”

Section: Introductionmentioning

confidence: 99%

Proliferative effects of melatonin on Schwann cells: implication for nerve regeneration following peripheral nerve injury

Chang

Liu

Hsu

et al. 2014

Activation of proliferation of Schwann cells is crucial for axonal guidance and successful nerve regeneration following peripheral nerve injury (PNI). Considering melatonin plays an important role in proliferative regulation of central glial cells, the present study determined whether melatonin can effectively promote Schwann cell proliferation and improve nerve regeneration after PNI. The spontaneous immortalized rat Schwann cell line (RSC 96 cells) was first analyzed by quantitative polymerase chain reaction (QPCR) to detect the potential existence of melatonin receptors. The melatonin receptor-mediated signaling responsible for proliferation was examined by measuring the phosphorylation of extracellular signal-regulated kinases (ERK1/2) pathway. The in vivo model of PNI was performed by the end-to-side neurorrhaphy. The quantity of Schwann cells as well as the number of re-innervated motor end plates (MEP) on target muscles was examined to represent the functional recovery of injured nerves. QPCR results indicated that MT1 is the dominant receptor in Schwann cells. Immunoblotting and proliferation assay revealed an enhanced phosphorylation of ERK1/2 and increased number of RSC 96 cells following melatonin administration. Nonselective melatonin receptor antagonist (luzindole) treatment significantly suppressed all the above findings, suggesting that the proliferative effects of melatonin were mediated by a receptor-dependent pathway. In vivo results corresponded well with in vitro findings in which melatonin effectively increased the amount of proliferated Schwann cells and re-innervated MEP on target muscles following PNI. As melatonin successfully improves nerve regeneration by promoting Schwann cell proliferation, therapeutic use of melatonin may thus serve as a promising strategy to counteract the PNI-induced neuronal disability.

“…In vertebrates, melatonin is mainly secreted by the pineal gland and retina during the dark phase of the photoperiod and is known to regulate the circadian rhythm, pattern of sleep, thermoregulation, reproduction and also the immune function [1, 2]. As regards its immunomodulatory actions in mammals and birds, in vivo administration of melatonin stimulates both innate and adaptive immunity responses [3–10]. Thus, antibody titres, antibody‐dependent cellular cytotoxicity (ADCC), natural killer (NK) cell activity, cytokine release, lymphocyte proliferation, antigen presentation, the number of granulocyte–macrophage colony forming units in the bone marrow and the ability of restoration after immunosuppression are some of the activities modified by melatonin treatments.…”

Section: Introductionmentioning

confidence: 99%

In vivo actions of melatonin on the innate immune parameters in the teleost fish gilthead seabream

Cuesta

Cerezuela

Meseguer

2008

Melatonin, a molecule produced in the pineal gland and retina of vertebrates, plays a major role in day-night circadian rhythms and other physiological processes, including the immune responses. Because little is known in this respect in fish, we have evaluated the in vivo role of melatonin in the main innate immune activities and the expression of immune-relevant genes in a teleost fish, the gilthead seabream (Sparus aurata L.). An intraperitoneal injection of 1 or 10 mg melatonin/kg of body weight produced a dose-time dependent increase in circulating melatonin serum levels. Several innate immune responses such as peroxidase, phagocytic, reactive oxygen intermediates and cell-mediated cytotoxic activities were significantly enhanced by the administration of melatonin at different sampling times. The expression of immune-relevant genes such as interleukin-1beta, major histocompatibility complex, virus-related response (interferon-regulatory factor-1 and Mx) and lymphocyte markers (immunoglobulin M and T-cell receptor for B and T lymphocytes, respectively), as analysed by semi-quantitative reverse transcription-polymerase chain reaction, was up-regulated in the head-kidney of melatonin-injected fish 1 and 3 days postinjection and decreased after 7 days. These data, together with our previous observations describing how photoperiod and in vitro melatonin treatment may affect seabream and sea bass immunology, confirm melatonin as a regulator of fish immunology. However, further studies are still needed to reveal the mechanisms underlying the direct or indirect interactions of melatonin with the fish immune system.