Salicylate-enhanced activation of transcription factors induced by interferon-gamma.
Salicylate enhanced the interferon-gamma-dependent activation of two transcription factors in a murine macrophage cell line: signal transducer and activator of transcription (STAT)1 and interferon-gamma-responsive factor 1. Salicylate alone did not activate these transcription factors. This enhancement was reflected by increased DNA-binding activities and was the consequence of prolonged tyrosine phosphorylation of these transcription factors following interferon-gamma treatment. However, salicylate did not directly inhibit protein-tyrosine phosphatase activity in nuclear extracts of interferon-gamma-treated cells. The enhanced activation of STAT1 resulted in increased induction of mRNA encoding interferon regulatory factor-1. These results not only demonstrate that aspirin and its metabolite salicylate may have pro-inflammatory as well as anti-inflammatory effects but also raise the possibility that new cellular targets may be identified for modulating the Janus kinase-STAT signalling pathway.
Chen
L C
LC
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Kepka-Lenhart
D
D
Wright
T M
TM
Morris
S M
SM
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor; D012459:Salicylates / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects*
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D012459:Salicylates; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D001241:Aspirin