The cutaneous serotoninergic/melatoninergic system: securing a place under the sun

Slominski, Andrzej; Wortsman, Jacobo; Tobin, Desmond J.

doi:10.1096/fj.04-2079rev

Cited by 355 publications

(498 citation statements)

References 168 publications

(314 reference statements)

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“…The exact source of the "UVinduced" serotonin in our system is not entirely clear. It is interesting to note that recent studies indicate that serotonin is produced by the skin (40). Whether its production is up-regulated following total body UV exposure remains to be seen.…”

Section: Discussionmentioning

confidence: 99%

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

Matsumura

Byrne

Nghiem

et al. 2006

The Journal of Immunology

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UV exposure suppresses the immune response to a variety of microbial, fungal, and viral Ags. In addition, UV radiation is a complete carcinogen and the immune suppression induced by UV radiation is a major risk factor for skin cancer induction. In this study, we examined the mechanisms underlying the induction of immune suppression and tolerance induction by UV radiation. Transferring lymph nodes cells from UV-irradiated, FITC-sensitized mice into normal recipients transferred immune tolerance. Contrary to expectations, the cell responsible was an FITC+, IL-10-secreting, CD19+, B220+ B cell. Because the lipid mediator of inflammation, platelet-activating factor (PAF) is released by UV-irradiated keratinocytes and is essential for the induction of immune suppression, we determined its role in tolerance induction. When UV-irradiated mice were injected with PCA 4248, a selective PAF receptor (PAFR) antagonist, transfer of tolerance was suppressed. However, immune suppression was not transferred when FITC+ cells from the draining lymph nodes of UV-irradiated, PAFR-deficient donor mice were injected into the recipients. Because PCA 4248 also blocks serotonin receptor binding, we measured the effect that blocking both serotonin and PAFR binding has on the transfer of immune suppression. Only when both PAF and serotonin binding were blocked could we inhibit tolerance induction. These data identify a novel function for PAF and serotonin in modulating immune function, the activation of immunoregulatory B cells.

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Section: Discussionmentioning

confidence: 99%

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

Matsumura

Byrne

Nghiem

et al. 2006

The Journal of Immunology

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“…In both cases, MUPP1 is removed far from its potential membrane partners, thus impeding any interaction with them. Regulation of the MT 1 /MUPP1 interaction is likely to occur under these circumstances, since functional MT 1 expression has been shown in keratinocytes (49) and mammary tumors (50). Recently, MUPP1 has been shown to be robustly up-regulated by hypertonicity and to be important in the osmotic stress response in tight junctions of kidney cells (51).…”

Section: Discussionmentioning

confidence: 99%

The PDZ Protein Mupp1 Promotes Gi Coupling and Signaling of the Mt1 Melatonin Receptor

Guillaume

Daulat

Maurice

et al. 2008

Journal of Biological Chemistry

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The concept of organized networks has emerged in the field of cellular signaling in the last few years. Assembling the different partners in close proximity optimizes the spatial and temporal organization and the specificity of the cellular response. The assembly of these multimolecular complexes occurs through the interaction of modular domains recognizing their target counterparts. PDZ domains are widely spread modules exhibiting this function. Data bank exploration with SMART (1) identifies 584 PDZ domains in 328 different proteins in the human genome.G protein-coupled receptors (GPCRs) 5 constitute the largest family of membrane receptors, and many of the more than 750 members have been shown to interact with PDZ domain-containing proteins, either constitutively or upon agonist activation (2). Binding of PDZ proteins to GPCRs has been reported to primarily regulate subcellular localization, trafficking, and stability of receptors (3). For instance, binding of MUPP1 and syntrophins to the ␥-aminobutyric acid type B (GABA B ) receptor and the ␣ 1D -adrenergic receptor, respectively, significantly increases receptor stability (4, 5). In other cases, PDZ scaffolds determine the subcellular localization of GPCRs (6) and receptor endocytosis as shown for PSD-95 and the 5-HT 2A serotonin and ␤ 1 -adrenergic receptors (7,8). PDZ proteins, such as NHERF and hScrib, are also important for the recycling of receptors to the cell surface (9 -11).Binding of PDZ proteins to GPCRs also modulates receptor signaling by assembling proteins involved in signal transduction. NHERF family proteins are known to regulate the activity of the Na ϩ /H ϩ exchanger through association with NHERF-1 (12) and to form a ternary complex with phospholipase C␤3 and GPCRs, which enhances the signaling efficiency of the receptor-mediated activation of the phospholipase C␤/Ca 2ϩ pathway (13-15). Binding of GIPC (GAIP-interacting protein, COOH terminus) to the COOH terminus of the D3 dopamine and the ␤ 1 -adrenergic receptor (16) decreased G␣ i -mediated signaling of these receptors most likely through RGS19, which binds to GIPC (17). Further examples of PDZ scaffolds that regulate GPCR signaling include a ternary complex formation around the PDZ scaffold MAGI-3, which binds to the GPCR frizzled-4 and Ltap to regulate the JNK signaling cascade (18), as well as PDZ-domain-containing Rho guanine nucleotide exchange factors that interact with lysophosphatidic acid 1 and 2 receptors to activate RhoA (19).

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“…Increasing evidence in the field suggests that melatonin acts at many extrapineal sites such as the gastrointestinal tract (11,12), the blood cell system (13), the retina (14), the bone marrow (15,16) and the skin (17)(18)(19)(20)(21)(22). In the epidermal keratinocytes, a constitutive and UV-induced melatonin metabolism has recently been described (23).…”

Section: Introductionmentioning

confidence: 99%

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Fischer

Żmijewski²,

Zbytek³

et al. 2006

Int J Oncol

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Abstract.Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10 -12 -10 -3 M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor ROR· by RT-PCR. Melatonin at pharmacological concentrations (10 -3 -10 -7 M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10 -12 -10 -10 M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor ROR· including its isoform ROR·4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.

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The cutaneous serotoninergic/melatoninergic system: securing a place under the sun

Cited by 355 publications

References 168 publications

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

The PDZ Protein Mupp1 Promotes Gi Coupling and Signaling of the Mt1 Melatonin Receptor

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

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