Inhibitors of Mitogen-Activated Protein Kinases Downregulate COX-2 Expression in Human Chondrocytes

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dc.contributor.author Nieminen, Riina -
dc.contributor.author Leinonen, Sari -
dc.contributor.author Lahti, Aleksi -
dc.contributor.author Vuolteenaho, Katriina -
dc.contributor.author Jalonen, Ulla -
dc.contributor.author Kankaanranta, Hannu -
dc.contributor.author Goldring, Mary B -
dc.contributor.author Moilanen, Eeva -
dc.date.accessioned 2012-06-17T20:14:12Z
dc.date.available 2012-06-15 10:33:50 -
dc.date.available 2012-06-17T20:14:12Z
dc.date.issued 2005 -
dc.identifier.issn 1466-1861 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/65872
dc.description Hindawi Open access -
dc.description.abstract Inducible prostaglandin synthase (cyclooxygenase-2, COX-2) is expressed in rheumatoid and osteoarthritic cartilage and produces high amounts of proinflammatory prostanoids in the joint. In the present study we investigated the effects of the inhibitors of mitogen-activated protein kinase (MAPK) pathways Erk1/2, p38, and JNK on COX-2 expression and prostaglandin E2 (PGE2) production in human chondrocytes. Proinflammatory cytokine IL-1β caused a transient activation of Erk1/2, p38, and JNK in immortalized human T/C28a2 chondrocytes and that was followed by enhanced COX-2 expression and PGE2 production. PD98059 (an inhibitor of Erk1/2 pathway) suppressed IL-1-induced COX-2 expression and PGE2 production in a dose-dependent manner, and seemed to have an inhibitory effect on COX-2 activity. SB203580 (an inhibitor of p38 pathway) but not its negative control compound SB202474 inhibited COX-2 protein and mRNA expression and subsequent PGE2 synthesis at micromolar drug concentrations. SP600125 (a recently developed JNK inhibitor) but not its negative control compound N1-methyl-1,9-pyrazolanthrone downregulated COX-2 expression and PGE2 formation in a dose-dependent manner. SP600125 did not downregulate IL-1-induced COX-2 mRNA expression when measured 2 h after addition of IL-1β but suppressed mRNA levels in the later time points suggesting post-transcriptional regulation. Our results suggest that activation of Erk1/2, p38, and JNK pathways belongs to the signaling cascades that mediate the upregulation of COX-2 expression and PGE2 production in human chondrocytes exposed to proinflammatory cytokine IL-1β. -
dc.language.iso en -
dc.title Inhibitors of Mitogen-Activated Protein Kinases Downregulate COX-2 Expression in Human Chondrocytes -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-634 -
dc.identifier.doi 10.1155/MI.2005.249 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Farmasia | en=Pharmacy| -
dc.journal.title Mediators of Inflammation -
dc.journal.volume 2005 -
dc.journal.number 5 -
dc.journal.volumepagerange 249-255 -
dc.oldstats 76 -

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