JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-<mml:math alttext="$gamma$"> <mml:mi>γ</mml:mi> </mml:math>-Induced iNOS Expression and NO Production in Macrophages
<p>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 inte...
| Format: | Article |
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| Language: | English |
| Published: |
Hindawi Limited
2006-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://www.hindawi.com/GetArticle.aspx?doi=10.1155/MI/2006/16161 |
| Summary: | <p>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-<mml:math alttext="$gamma$"> <mml:mi>γ</mml:mi> </mml:math> (IFN-<mml:math alttext="$gamma$"> <mml:mi>γ</mml:mi> </mml:math>). JAK inhibitors AG-490 and WHI-P154 decreased IFN-<mml:math alttext="$gamma$"> <mml:mi>γ</mml:mi> </mml:math>-induced nuclear levels of signal transducer and activator of transcription 1<mml:math alttext="$alpha$"> <mml:mi>α</mml:mi> </mml:math> (STAT1<mml:math alttext="$alpha$"> <mml:mi>α</mml:mi> </mml:math>). 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-<mml:math alttext="$gamma$"> <mml:mi>γ</mml:mi> </mml:math>-stimulated macrophages.</p> |
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| ISSN: | 0962-9351 |