Abstract
Activin A is a multifunctional cytokine essential for cell differentiation and apoptosis including erythroid cell differentiation in the bone marrow. In addition, activin A is induced by inflammation and exerts anti-inflammatory effects. However, the mechanism of activin A induction is still unclear, especially by inflammatory processes. Here we show that activin A secretion from monocytes and bone marrow stromal fibroblasts, its major sources in the bone marrow, is markedly enhanced by cognate interaction with activated T cells. This process is mediated by CD40/CD40 ligand interaction as well as concomitantly secreted T cell-derived cytokines, granulocyte macrophage-colony stimulating factor, and interferon-gamma. Furthermore, stromal fibroblasts as well as monocytes provide a costimulatory signal to anti-CD3-treated T cells via CD80 and CD86 to maintain the enhanced activin A production. These findings suggest that activin A is potently induced in the bone marrow and may play a role in the suppression of inflammatory or immune processes.
MeSH terms
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Activins / biosynthesis
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Activins / genetics
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Activins / metabolism*
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Animals
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Antigens, CD / physiology
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B7-1 Antigen / physiology
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B7-2 Antigen
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CD3 Complex / immunology
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CD40 Antigens / genetics
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CD40 Antigens / physiology
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CD40 Ligand / physiology
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COS Cells
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Chlorocebus aethiops
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Coculture Techniques
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Fibroblasts / metabolism*
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Follistatin
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology
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Humans
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Inhibin-beta Subunits / biosynthesis
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Inhibin-beta Subunits / genetics
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Inhibin-beta Subunits / metabolism*
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Interferon-gamma / pharmacology
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Interferon-gamma / physiology
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Interleukin-1 / pharmacology
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Interleukin-2 / pharmacology
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Lymphocyte Activation*
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Lymphokines / physiology
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Membrane Glycoproteins / physiology
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Monocytes / metabolism*
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Muromonab-CD3 / pharmacology
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Phytohemagglutinins / pharmacology
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Recombinant Proteins / pharmacology
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Stromal Cells / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Transfection
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Vesicular stomatitis Indiana virus / physiology
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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CD3 Complex
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CD40 Antigens
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CD86 protein, human
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Follistatin
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Interleukin-1
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Interleukin-2
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Lymphokines
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Membrane Glycoproteins
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Muromonab-CD3
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Phytohemagglutinins
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Recombinant Proteins
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activin A
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Activins
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CD40 Ligand
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor
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Inhibin-beta Subunits