Interferon-alpha inhibits interleukin-3-induced proliferation of Ba/F3 cells in a protein kinase R-dependent manner.
We have previously shown that interferon-alpha (IFN-alpha) inhibits proliferation of Ba/F3 cells by interfering with the action of the mitogen interleukin-3 (IL-3) [Cell Signal 11 (1999) 769]. Here, we have characterised the role of protein kinase R (PKR), an IFN-alpha-inducible enzyme, in the mediation of IL-3-antagonistic IFN-alpha effects. Downregulation of PKR expression by antisense oligonucleotide treatment blocked IFN-alpha-induced growth inhibition. Reduction of PKR levels and overexpression of a dominant-negative PKR mutant correlated with diminished inhibitory IFN-alpha effects on the IL-3-dependent expression of a luciferase reporter construct, GAS-luc. Furthermore, increased nuclear levels of STAT1 (bound in ISGF3 complexes) were observed in PKR-depleted cells cultured with or without IFN-alpha. Together, our data indicate an essential role of PKR in the mediation of IL-3-antagonistic IFN-alpha effects on Ba/F3 cells. They also suggests that activation of STAT1, an essential mediator of IFN effects, is insufficient for growth inhibition if PKR is not expressed.
Schröder
Katrin
K
Division of Gastroenterology, Department of Medicine, Medical Faculty, University of Rostock, E.-Heydemann-Str. 6, 18057 Rostock, Germany.
Jaster
Robert
R
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D016898:Interferon-alpha / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D007377:Interleukin-3; D020319:Oligodeoxyribonucleotides, Antisense; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D019892:eIF-2 Kinase