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JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-gamma-induced iNOS Expression and NO Production in Macrophages

JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-gamma-induced iNOS Expression and NO Production in Macrophages

Outi Sareila, Riku Korhonen, Outi Kärpänniemi, Riina Nieminen, Hannu Kankaanranta, Eeva Moilanen

Mediators Inflamm. 2006;2006(2):16161.

PMID: 16883061

Abstract:

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-gamma (IFN-gamma). JAK inhibitors AG-490 and WHI-P154 decreased IFN-gamma-induced nuclear levels of signal transducer and activator of transcription 1alpha (STAT1alpha). JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA expression and NO production in a concentration-dependent manner. Neither of the JAK inhibitors affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAK-STAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN-gamma-stimulated macrophages.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP211555043-B	WHI-P154		211555-04-3	Price

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