A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Bacterial ligand of TLR2 signals Stat activation via induction of IRF1/2 and interferon-alpha production
Tekijät: Liljeroos M, Vuolteenaho R, Rounioja S, Henriques-Normark B, Hallman M, Ojaniemi M
Kustannuspaikka: England
Julkaisuvuosi: 2008
Tietokannassa oleva lehden nimi: Cellular signalling
Lehden akronyymi: Cell.Signal.
Vuosikerta: 20
Numero: 10
Aloitussivu: 1873
Lopetussivu: 1881
Tiivistelmä
Both type I interferons (IFNs) and interferon regulatory factors (IRFs) are well characterized in viral infections, whereas they are far less studied in bacterially activated toll-like receptor (TLR) pathways. Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses. In mouse macrophages, IRF2 was activated by lipoteichoic acid (LTA) of Staphylococcus aureus, resulting in up-regulation of IRF1 and rapid secretion of IFN-alpha. In addition, LTA-induced activation of Signal transducers and activators of transcription 1 (Stat1) and Stat3 via IRF2. The secretion of IFN-alpha was reduced in IRF2-silenced macrophages, resulting in a disappearance of tyrosine-phosphorylated Stat3 and a reduction of pro-inflammatory responses, despite induction of Mal adapter protein. These results provide a mechanistic insight into the pro-inflammatory responses against S. aureus LTA in mouse macrophages. IRFs can be intersecting factors of viral and bacterial responses in activated TLR signalling pathways.
Both type I interferons (IFNs) and interferon regulatory factors (IRFs) are well characterized in viral infections, whereas they are far less studied in bacterially activated toll-like receptor (TLR) pathways. Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses. In mouse macrophages, IRF2 was activated by lipoteichoic acid (LTA) of Staphylococcus aureus, resulting in up-regulation of IRF1 and rapid secretion of IFN-alpha. In addition, LTA-induced activation of Signal transducers and activators of transcription 1 (Stat1) and Stat3 via IRF2. The secretion of IFN-alpha was reduced in IRF2-silenced macrophages, resulting in a disappearance of tyrosine-phosphorylated Stat3 and a reduction of pro-inflammatory responses, despite induction of Mal adapter protein. These results provide a mechanistic insight into the pro-inflammatory responses against S. aureus LTA in mouse macrophages. IRFs can be intersecting factors of viral and bacterial responses in activated TLR signalling pathways.
Avainsanat:
Animals, Cell Line, inflammation, Interferon-alpha/biosynthesis/secretion, Interferon-beta/secretion, Interferon-gamma/secretion, Interferon Regulatory Factor-1/metabolism, Interferon Regulatory Factor-2/metabolism, Ligands, Lipopolysaccharides/pharmacology, Macrophages/drug effects/enzymology/secretion, Mice, Myeloid Differentiation Factor 88/metabolism, Protein-Tyrosine Kinases/metabolism, Signal Transduction/drug effects, Staphylococcus aureus/chemistry, STAT1 Transcription Factor/metabolism, STAT3 Transcription Factor/metabolism, STAT Transcription Factors/metabolism, Teichoic Acids/pharmacology, Toll-Like Receptor 2/metabolism, Transcription Factors/metabolism
Turun yliopiston Tutkimustietojärjestelmän portaali