Abstract
FcepsilonRI expression and function is a central aspect of allergic disease. Using bone marrow-derived mouse mast cell populations, we have previously shown that the Th2 cytokine IL-4 inhibits FcepsilonRI expression and function. In the current study we show that the Th2 cytokine IL-10 has similar regulatory properties, and that it augments the inhibitory effects of IL-4. FcepsilonRI down-regulation was functionally significant, as it diminished inflammatory cytokine production and IgE-mediated FcepsilonRI up-regulation. IL-10 and IL-4 reduced FcepsilonRI beta protein expression without altering the alpha or gamma subunits. The ability of IL-4 and IL-10 to alter FcepsilonRI expression by targeting the beta-chain, a critical receptor subunit known to modulate receptor expression and signaling, suggests the presence of a Th2 cytokine-mediated homeostatic network that could serve to both initiate and limit mast cell effector function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Animals
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Cells, Cultured
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Drug Synergism
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Immunoglobulin E / physiology
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Interleukin-10 / physiology*
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Interleukin-4 / pharmacology
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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 BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Protein Subunits / antagonists & inhibitors*
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Protein Subunits / biosynthesis*
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Protein Subunits / genetics
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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Receptors, IgE / antagonists & inhibitors*
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Receptors, IgE / biosynthesis*
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Receptors, IgE / genetics
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STAT6 Transcription Factor
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Trans-Activators / deficiency
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Trans-Activators / genetics
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Trans-Activators / physiology
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Protein Subunits
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RNA, Messenger
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Receptors, IgE
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Trans-Activators
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Interleukin-10
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Interleukin-4
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Immunoglobulin E