JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
Sareila, Outi; Korhonen, Riku; Kärpänniemi, Outi; Nieminen, Riina; Kankaanranta, Hannu; Moilanen, Eeva (2006)
2006
Mediators of Inflammation 2006
16161
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Julkaisun pysyvä osoite on
http://urn.fi/urn:nbn:uta-3-733
http://urn.fi/urn:nbn:uta-3-733
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Hindawi Open access
Tiivistelmä
In inflammation, inducible nitric oxide synthase (iNOS) produces nitric oxide (NO), which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK) inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon-γ (IFN-γ). JAK inhibitors AG-490 andWHI-P154 decreased IFN-γ-induced nuclear levels of signal transducer and activator of transcription 1α (STAT1α). JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA expression and NO production in a concentration-dependentmanner. Neither of the JAK inhibitors
affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAKSTAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN-γ-stimulated macrophages.
affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAKSTAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN-γ-stimulated macrophages.
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