Abstract
Nuclear receptor 4a3 (Nr4a3) is a transcription factor implicated in various settings such as vascular biology and inflammation. We have recently shown that mast cells dramatically upregulate Nuclear receptor 4a3 upon activation, and here we investigated the functional impact of Nuclear receptor 4a3 on mast cell responses. We show that Nuclear receptor 4a3 is involved in the regulation of cytokine/chemokine secretion in mast cells following activation via the high affinity IgE receptor. Moreover, Nuclear receptor 4a3 negatively affects the transcript and protein levels of mast cell tryptase as well as the mast cell's responsiveness to allergen. Together, these findings identify Nuclear receptor 4a3 as a novel regulator of mast cell function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Blotting, Western
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Proliferation
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Cells, Cultured
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Chemokines / genetics
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Chemokines / metabolism
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Cytokines / genetics
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Cytokines / metabolism
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Cytoplasmic Granules / drug effects
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Cytoplasmic Granules / immunology
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Cytoplasmic Granules / metabolism*
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DNA-Binding Proteins / physiology*
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Immunoglobulin E / pharmacology
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Mast Cells / cytology
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Mast Cells / drug effects
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Mast Cells / immunology
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Mast Cells / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nerve Tissue Proteins / physiology*
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Receptors, IgE / genetics
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Receptors, IgE / metabolism
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Receptors, Steroid / physiology*
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Receptors, Thyroid Hormone / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Tryptases / genetics
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Tryptases / metabolism
Substances
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Chemokines
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Cytokines
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DNA-Binding Proteins
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NF-kappa B
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Nerve Tissue Proteins
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Nr4a3 protein, mouse
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RNA, Messenger
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Receptors, IgE
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Receptors, Steroid
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Receptors, Thyroid Hormone
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Immunoglobulin E
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Tryptases
Grants and funding
This work was supported by grants from: Magnus Bergvall Foundation, The Swedish Cancer Foundation, The Swedish Research Council, Formas, King Gustaf V’s 80-year Anniversary Fund, and Fundación Española para la Ciencia y la Tecnología y Ministerio de Educación, Cultura y Deporte. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.