Abstract
Interleukin-6 (IL-6) is active in the early steps of T cell activation and confers IL-2 responsiveness. In this work, we used EL4 T lymphoma to identify IL-6 target genes in T cells. By differential screening of a cDNA library, we found that IL-6 induced the expression of Ly-6A/E, a GPI-anchored cell surface protein reported to be a regulator of T cell activation. In addition to IL-6, IL-9 and IFN-gamma induced Ly-6A/E expression in EL4 and BW5147 cells. We showed that both IL-6 and IL-9 mediated the transcriptional activation of Ly-6A/E through a GAS element in the Ly-6A/E promoter, which was able to bind STAT1 and STAT3, transcription factors activated by these cytokines. IL-6 had a similar effect in freshly isolated normal T cells, and dramatically increased their proliferation upon Ly-6A/E stimulation. Taken together, our data suggest that Ly-6A/E induction takes part in the T cell activation program initiated by IL-6.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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Animals
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Antigens, Ly / biosynthesis
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Antigens, Ly / genetics*
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Humans
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Interleukin-6 / pharmacology*
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Interleukin-9 / pharmacology*
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Lymphocyte Activation
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Lymphoma, T-Cell / immunology
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics*
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Mice
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Mice, Inbred DBA
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Phloretin / pharmacology
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Polymerase Chain Reaction
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Promoter Regions, Genetic
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Protein Kinase C / antagonists & inhibitors
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Receptors, Interleukin / genetics
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Receptors, Interleukin / physiology*
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Receptors, Interleukin-9
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
Substances
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Antigens, Ly
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IL9R protein, human
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Interleukin-6
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Interleukin-9
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Ly6a protein, mouse
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Membrane Proteins
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Receptors, Interleukin
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Receptors, Interleukin-9
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Recombinant Proteins
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Protein Kinase C
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Phloretin