Abstract
This report shows that melatonin enhances IL-6 production by U937 cells via a nuclear receptor-mediated mechanism. Resting U937 cells only express membrane (mt1) melatonin receptors. In these cells, melatonin did not modify basal production of IL-6 or when activated by PMA plus lipopolysaccharide, a treatment that downregulates the expression of mt1 receptor. However, in U937 cells activated with IFN-gamma, which induces the expression of the ROR alpha 1 and ROR alpha 2 nuclear receptors and represses the expression of the mt1 receptor, melatonin can activate IL-6 production. These results show that the expression of nuclear melatonin receptor but not membrane receptors is sufficient for melatonin to activate cytokine production in human lymphocytic and monocytic cell lines.
Copyright 2000 S. Karger AG, Basel
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Down-Regulation
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Drug Synergism
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Humans
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Interferon-gamma / pharmacology
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Interleukin-6 / biosynthesis*
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Lipopolysaccharides / pharmacology
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Melatonin / metabolism*
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RNA, Messenger / metabolism
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Cytoplasmic and Nuclear / drug effects
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Cytoplasmic and Nuclear / physiology*
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Receptors, Melatonin
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Tetradecanoylphorbol Acetate / pharmacology
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U937 Cells
Substances
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Interleukin-6
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Lipopolysaccharides
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Receptors, Melatonin
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Interferon-gamma
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ROR1 protein, human
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ROR2 protein, human
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors
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Melatonin
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Tetradecanoylphorbol Acetate