Protein kinase A regulates GATA-3-dependent activation of IL-5 gene expression in Th2 cells.
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.
Klein-Hessling
Stefan
S
Department of Molecular Pathology, Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany.
Jha
Mithilesh Kumar
MK
Santner-Nanan
Brigitte
B
Berberich-Siebelt
Friederike
F
Baumruker
Thomas
T
Schimpl
Anneliese
A
Serfling
Edgar
E
D000818:Animals; D020134:Catalytic Domain / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D013449:Sulfonamides; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D015848:Interleukin-5; D007546:Isoquinolines; D021122:Protein Subunits; D013449:Sulfonamides; D015534:Trans-Activators; D015847:Interleukin-4; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide