Cargando…
Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor
In inflammatory processes, the p38 mitogen-activated protein kinase (MAPK) signal transduction route regulates production and expression of cytokines and other inflammatory mediators. Tumor necrosis factor α (TNF-α) is a pivotal cytokine in rheumatoid arthritis and its production in macrophages is u...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2004
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC464924/ https://www.ncbi.nlm.nih.gov/pubmed/15225374 http://dx.doi.org/10.1186/ar1204 |
_version_ | 1782121612761366528 |
---|---|
author | Westra, Johanna Doornbos-van der Meer, Berber de Boer, Peter van Leeuwen, Miek A van Rijswijk, Martin H Limburg, Pieter C |
author_facet | Westra, Johanna Doornbos-van der Meer, Berber de Boer, Peter van Leeuwen, Miek A van Rijswijk, Martin H Limburg, Pieter C |
author_sort | Westra, Johanna |
collection | PubMed |
description | In inflammatory processes, the p38 mitogen-activated protein kinase (MAPK) signal transduction route regulates production and expression of cytokines and other inflammatory mediators. Tumor necrosis factor α (TNF-α) is a pivotal cytokine in rheumatoid arthritis and its production in macrophages is under control of the p38 MAPK route. Inhibition of the p38 MAPK route may inhibit production not only of TNF-α, but also of other inflammatory mediators produced by macrophages, and indirectly of inflammatory mediators by other cells induced by TNF-α stimulation. Here we investigate the effects of RWJ 67657, a p38 MAPK inhibitor, on mRNA expression and protein production of TNF-α and other inflammatory mediators, in monocyte-derived macrophages. A strong inhibition of TNF-α was seen at pharmacologically relevant concentrations of RWJ 67657, but also inhibition of mRNA expression of IL-1β, IL-8, and cyclooxygenase-2 was shown. Furthermore, it was shown that monocyte-derived macrophages have a high constitutive production of matrix metalloproteinase 9, which is not affected by p38 MAPK inhibition. The results presented here may have important implications for the treatment of rheumatoid arthritis. |
format | Text |
id | pubmed-464924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-4649242004-07-16 Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor Westra, Johanna Doornbos-van der Meer, Berber de Boer, Peter van Leeuwen, Miek A van Rijswijk, Martin H Limburg, Pieter C Arthritis Res Ther Research Article In inflammatory processes, the p38 mitogen-activated protein kinase (MAPK) signal transduction route regulates production and expression of cytokines and other inflammatory mediators. Tumor necrosis factor α (TNF-α) is a pivotal cytokine in rheumatoid arthritis and its production in macrophages is under control of the p38 MAPK route. Inhibition of the p38 MAPK route may inhibit production not only of TNF-α, but also of other inflammatory mediators produced by macrophages, and indirectly of inflammatory mediators by other cells induced by TNF-α stimulation. Here we investigate the effects of RWJ 67657, a p38 MAPK inhibitor, on mRNA expression and protein production of TNF-α and other inflammatory mediators, in monocyte-derived macrophages. A strong inhibition of TNF-α was seen at pharmacologically relevant concentrations of RWJ 67657, but also inhibition of mRNA expression of IL-1β, IL-8, and cyclooxygenase-2 was shown. Furthermore, it was shown that monocyte-derived macrophages have a high constitutive production of matrix metalloproteinase 9, which is not affected by p38 MAPK inhibition. The results presented here may have important implications for the treatment of rheumatoid arthritis. BioMed Central 2004 2004-06-21 /pmc/articles/PMC464924/ /pubmed/15225374 http://dx.doi.org/10.1186/ar1204 Text en Copyright © 2004 Westra et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Article Westra, Johanna Doornbos-van der Meer, Berber de Boer, Peter van Leeuwen, Miek A van Rijswijk, Martin H Limburg, Pieter C Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor |
title | Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor |
title_full | Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor |
title_fullStr | Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor |
title_full_unstemmed | Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor |
title_short | Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor |
title_sort | strong inhibition of tnf-α production and inhibition of il-8 and cox-2 mrna expression in monocyte-derived macrophages by rwj 67657, a p38 mitogen-activated protein kinase (mapk) inhibitor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC464924/ https://www.ncbi.nlm.nih.gov/pubmed/15225374 http://dx.doi.org/10.1186/ar1204 |
work_keys_str_mv | AT westrajohanna stronginhibitionoftnfaproductionandinhibitionofil8andcox2mrnaexpressioninmonocytederivedmacrophagesbyrwj67657ap38mitogenactivatedproteinkinasemapkinhibitor AT doornbosvandermeerberber stronginhibitionoftnfaproductionandinhibitionofil8andcox2mrnaexpressioninmonocytederivedmacrophagesbyrwj67657ap38mitogenactivatedproteinkinasemapkinhibitor AT deboerpeter stronginhibitionoftnfaproductionandinhibitionofil8andcox2mrnaexpressioninmonocytederivedmacrophagesbyrwj67657ap38mitogenactivatedproteinkinasemapkinhibitor AT vanleeuwenmieka stronginhibitionoftnfaproductionandinhibitionofil8andcox2mrnaexpressioninmonocytederivedmacrophagesbyrwj67657ap38mitogenactivatedproteinkinasemapkinhibitor AT vanrijswijkmartinh stronginhibitionoftnfaproductionandinhibitionofil8andcox2mrnaexpressioninmonocytederivedmacrophagesbyrwj67657ap38mitogenactivatedproteinkinasemapkinhibitor AT limburgpieterc stronginhibitionoftnfaproductionandinhibitionofil8andcox2mrnaexpressioninmonocytederivedmacrophagesbyrwj67657ap38mitogenactivatedproteinkinasemapkinhibitor |