Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system

Carrillo-Vico, Antonio; Garcı́a-Pergañeda, Antonio; Naji, Latifa; Calvo, Juan R.; Romero, M.; Guerrero, Juan M.

doi:10.1007/s00018-003-3207-4

Cited by 124 publications

(93 citation statements)

References 54 publications

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“…These data are in accordance with reports of CarrilloVico et al [22,29] , who suggested that IL-2 secretion by lymphocytes could be the marker of an autocrine action of melatonin. The function of MT1R and MT2R in target tissues was derived primarily from pharmacological studies using 2 prototype melatonin receptor antagonists, luzindole and 4P-PDOT [14,30] ; hence, we used a similar approach for the present study.…”

Section: Discussionsupporting

confidence: 82%

Melatonin Membrane Receptor Type MT1 Modulates Cell-Mediated Immunity in the Seasonally Breeding Tropical Rodent <i>Funambulus pennanti</i>

Ahmad

Haldar²,

Gupta³

2011

Neuroimmunomodulation

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Objective: Despite the evidence for melatonin membrane receptors (MT1R and MT2R) on lymphoid tissues in a wide range of seasonal breeders, their specific potency has never been compared and correlated with cell-mediated immunity. Methods: We used luzindole, a nonselective MT2R antagonist, and 4-phenyl-2-propionamidotetralin (4P-PDOT), a selective MT2R antagonist, to assess the potency of the melatonin receptors MT1 and MT2 in melatonin-induced immunity under both in vivo as well as in vitro conditions. Results: Physiological doses (25 µg/100 g body weight in vivo and 100 and 500 pg/ml in vitro) of melatonin upregulated both MT1R and MT2R expression as well as splenocyte proliferation, while higher doses (100 and 500 µg/100 g body weight in vivo and 1 ng/ml in vitro) downregulated splenocyte proliferation and the expression of both receptors. Luzindole antagonized the expression of both MT1R and MT2R in a dose-dependent manner under in vivo as well as in vitro conditions, while 4P-PDOT blocked the expression of MT2R only during both experimental conditions. Splenocyte proliferation and IL-2 secretion (in vitro) followed the MT1R expression pattern, while the MT2R expression pattern showed no definite relation with either splenocyte proliferation or IL-2 secretion under in vivo and in vitro conditions. Conclusion: Immune function in tropical rodents is directly regulated by melatonin via its high-affinity membrane receptor MT1. MT1R plays a directive role in mediating splenocyte proliferation and IL-2 release, while the MT2R subtype appears not to be required for the immunoenhancing role of melatonin.

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Section: Discussionsupporting

confidence: 82%

Melatonin Membrane Receptor Type MT1 Modulates Cell-Mediated Immunity in the Seasonally Breeding Tropical Rodent <i>Funambulus pennanti</i>

Ahmad

Haldar²,

Gupta³

2011

Neuroimmunomodulation

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“…The RT-PCR primers conditions for common RORα fragment and RORα1-4 isoforms were as described (common fragment, ref. 47 ; isoforms, ref. 45 ).…”

Section: Discussionmentioning

confidence: 99%

On the Role of Melatonin in Skin Physiology and Pathology

Słomiński

Fischer

Żmijewski

et al. 2005

ENDO

228

281

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Melatonin has been experimentally implicated in skin functions such as hair growth cycling, fur pigmentation, and melanoma control, and melatonin receptors are expressed in several skin cells including normal and malignant keratinocytes, melanocytes, and fibroblasts. Melatonin is also able to suppress ultraviolet (UV)-induced damage to skin cells and shows strong antioxidant activity in UV exposed cells. Moreover, we recently uncovered expression in the skin of the biochemical machinery involved in the sequential transformation of L-tryptophan to serotonin and melatonin. Existence of the biosynthetic pathway was confirmed by detection of the corresponding genes and proteins with actual demonstration of enzymatic activities for tryptophan hydroxylase, serotonin Nacetyl-transferase, and hydroxyindole-O-methyltransferase in extracts from skin and skin cells. Initial evidence for in vivo synthesis of melatonin and its metabolism was obtained in hamster skin organ culture and in one melanoma line. Therefore, we propose that melatonin (synthesized locally or delivered topically) could counteract or buffer external (environmental) or internal stresses to preserve the biological integrity of the organ and to maintain its homeostasis. Furthermore, melatonin could have a role in protection against solar radiation or even in the management of skin diseases.

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“…The presence of receptors in the human immune system was first shown by the demonstration of 2-[ 125 I]iodomelatonin binding sites in peripheral blood mononuclear cells (PBMCs) (LopezGonzalez et al, 1993). Membrane-bound melatonin receptors have since been characterized in thymus and spleen of many species (Carrillo-Vico et al, 2003b) as well as in peritoneal macrophages (Garcia-Perganeda et al, 1999). In mammals, membrane-bound melatonin receptors are distinguished pharmacologically as subtypes MT 1 and MT 2 , and are members of the G-protein-coupled receptor superfamily (Dubocovich, 1995).…”

mentioning

confidence: 99%

Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL‐2 production

Lardone

Carrillo-Vico

Naranjo

et al. 2005

Journal Cellular Physiology

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Human lymphocytes have recently been described as an important physiological source of melatonin (N-acetyl-5-methoxytryptamine), which could be involved in the regulation of the human immune system. On the other hand, stimulation of IL-2 production by exogenous melatonin has been shown in the Jurkat human lymphocytic cell line. Furthermore, both melatonin membrane and nuclear receptors are present in these cells. In this study, we show that the necessary machinery to synthesize melatonin is present and active in resting and stimulated Jurkat cells. Accordingly, we have found that cells synthesize and release melatonin in both conditions. Therefore, we investigated whether endogenous melatonin produced by Jurkat cells was involved in the regulation of IL-2 production. When melatonin membrane and nuclear receptors were blocked using specific antagonists, luzindole and CGP 55644, respectively, we found that IL-2 production decreased, and this drop was reverted by exogenous melatonin. Additionally, PHA activation of Jurkat cells changed the profile of melatonin nuclear receptor mRNA expression. A previous study showed that exogenous melatonin is able to counteract the decrease in IL-2 production caused by prostaglandin E2 (PGE2) in human lymphocytes via its membrane receptor. In our model, when we blocked the melatonin membrane receptor with luzindole, the inhibitory effect of PGE2 on IL-2 production was higher. Therefore, we have demonstrated the physiological role of endogenous melatonin in this cell line. These findings indicate that endogenous melatonin synthesized by human T cells would contribute to regulation of its own IL-2 production, acting as an intracrine, autocrine, and/or paracrine substance.

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Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system

Cited by 124 publications

References 54 publications

Melatonin Membrane Receptor Type MT1 Modulates Cell-Mediated Immunity in the Seasonally Breeding Tropical Rodent <i>Funambulus pennanti</i>

Melatonin Membrane Receptor Type MT1 Modulates Cell-Mediated Immunity in the Seasonally Breeding Tropical Rodent <i>Funambulus pennanti</i>

On the Role of Melatonin in Skin Physiology and Pathology

Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL‐2 production

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