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

Nieminen, Riina; Leinonen, Sari; Lahti, Aleksi; Vuolteenaho, Katriina; Jalonen, Ulla; Kankaanranta, Hannu; Goldring, Mary B; Moilanen, Eeva (2005)

 
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Nieminen, Riina
Leinonen, Sari
Lahti, Aleksi
Vuolteenaho, Katriina
Jalonen, Ulla
Kankaanranta, Hannu
Goldring, Mary B
Moilanen, Eeva
2005

Mediators of Inflammation 2005 5
249-255
This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
doi:10.1155/MI.2005.249
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https://urn.fi/urn:nbn:uta-3-634

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Hindawi Open access
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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.
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Kalevantie 5
PL 617
33014 Tampereen yliopisto
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