JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2006-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/MI/2006/16161 |
| Summary: | 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 and WHI-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-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-γ-stimulated macrophages. |
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| ISSN: | 0962-9351 1466-1861 |