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...

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Autores principales: Sareila, Outi, Korhonen, Riku, Kärpänniemi, Outi, Nieminen, Riina, Kankaanranta, Hannu, Moilanen, Eeva
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2006
Materias:
Research Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592588/
https://www.ncbi.nlm.nih.gov/pubmed/16883061
http://dx.doi.org/10.1155/MI/2006/16161
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author Sareila, Outi
Korhonen, Riku
Kärpänniemi, Outi
Nieminen, Riina
Kankaanranta, Hannu
Moilanen, Eeva
author_facet Sareila, Outi
Korhonen, Riku
Kärpänniemi, Outi
Nieminen, Riina
Kankaanranta, Hannu
Moilanen, Eeva
author_sort Sareila, Outi
collection PubMed
description 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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spelling pubmed-15925882006-10-23 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 Mediators Inflamm Research Communication 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. Hindawi Publishing Corporation 2006 2006-03-19 /pmc/articles/PMC1592588/ /pubmed/16883061 http://dx.doi.org/10.1155/MI/2006/16161 Text en Copyright © 2006 Outi Sareila et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Communication
Sareila, Outi
Korhonen, Riku
Kärpänniemi, Outi
Nieminen, Riina
Kankaanranta, Hannu
Moilanen, Eeva
JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
title JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
title_full JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
title_fullStr JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
title_full_unstemmed JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
title_short JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages
title_sort jak inhibitors ag-490 and whi-p154 decrease ifn-γ-induced inos expression and no production in macrophages
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592588/
https://www.ncbi.nlm.nih.gov/pubmed/16883061
http://dx.doi.org/10.1155/MI/2006/16161
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