Abstract
Treatment of Th cells with compounds that elevate cAMP levels augments Th2-type lymphokine expression, in particular the synthesis of IL-5. Using primary murine CD4(+) T lymphocytes, we show in this study that inhibition of protein kinase A (PKA) activity in Th2 effector cells impairs IL-5 synthesis, whereas the expression of PKA catalytic subunit alpha enhances IL-5 synthesis in Th0 cells. In addition, we observed by coexpression of PKA catalytic subunit and GATA-3 in Th1 cells that the stimulatory effect of PKA is dependent on GATA-3 activity. These data demonstrate that activation of PKA in Th effector cells induces the IL-5 gene expression in a GATA-3-dependent manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Catalytic Domain / genetics
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Catalytic Domain / immunology
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Cell Line
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Cells, Cultured
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclic AMP-Dependent Protein Kinases / physiology*
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DNA-Binding Proteins / physiology*
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Enzyme Inhibitors / pharmacology
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GATA3 Transcription Factor
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Gene Expression Regulation / immunology*
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Humans
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Interleukin-4 / biosynthesis
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Interleukin-5 / biosynthesis*
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Interleukin-5 / genetics*
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Isoquinolines / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Mutation
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Protein Subunits / biosynthesis
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Protein Subunits / genetics
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Sulfonamides*
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / enzymology
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Th2 Cells / immunology*
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Th2 Cells / metabolism*
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Trans-Activators / physiology*
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Transfection
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Tumor Cells, Cultured
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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DNA-Binding Proteins
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Enzyme Inhibitors
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GATA3 Transcription Factor
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GATA3 protein, human
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Gata3 protein, mouse
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Interleukin-5
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Isoquinolines
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Protein Subunits
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Sulfonamides
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Trans-Activators
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Interleukin-4
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide