Protein kinase A regulates GATA-3-dependent activation of IL-5 gene expression in Th2 cells

J Immunol. 2003 Mar 15;170(6):2956-61. doi: 10.4049/jimmunol.170.6.2956.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalytic Domain / genetics
  • Catalytic Domain / immunology
  • Cell Line
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • DNA-Binding Proteins / physiology*
  • Enzyme Inhibitors / pharmacology
  • GATA3 Transcription Factor
  • Gene Expression Regulation / immunology*
  • Humans
  • Interleukin-4 / biosynthesis
  • Interleukin-5 / biosynthesis*
  • Interleukin-5 / genetics*
  • Isoquinolines / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Mutation
  • Protein Subunits / biosynthesis
  • Protein Subunits / genetics
  • Sulfonamides*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / enzymology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*
  • Trans-Activators / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Gata3 protein, mouse
  • Interleukin-5
  • Isoquinolines
  • Protein Subunits
  • Sulfonamides
  • Trans-Activators
  • Interleukin-4
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide