Prostaglandin D2 enhances interleukin -1beta-induced cyclooxygenase-2 expression in osteoarthritic cartilage
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POSTER PRESENTATION
Open Access
Prostaglandin D2 enhances interleukin-1betainduced cyclooxygenase-2 expression in osteoarthritic cartilage N Zayed*, F E El Mansouri, N Chabane, J Martel-Pelletier, J P Pelletier, H Fahmi From 5th European Workshop on Immune-Mediated Inflammatory Diseases Sitges-Barcelona, Spain. 1-3 December 2010 Objective To investigate the effects of prostaglandin D2 (PGD2) on interleukin-1beta (IL-1beta)-induced cyclooxygenase (COX)-2 expression in human cartilage and the signalling pathways involved in these effects. Methods Chondrocytes were stimulated with IL-1 in the presence or absence of PGD2, and expression of COX-2 protein was evaluated by western-blotting. Messenger RNA (mRNA) expression was analyzed by real-time reverse transcription-polymerase chain reaction. The role of the PGD2 receptors D prostanoid receptor 1 (DP1) and chemoattractant receptor-like molecule expressed on Th2 cells (CRTH2) was evaluated using specific agonists.
Conclusion PGD2 stimulates IL-1-induced production of COX-2 by chondrocytes through the CRTH2/PIP2/PKC signalling pathway. Published: 25 November 2010
doi:10.1186/1479-5876-8-S1-P61 Cite this article as: Zayed et al.: Prostaglandin D2 enhances interleukin1beta- induced cyclooxygenase-2 expression in osteoarthritic cartilage. Journal of Translational Medicine 2010 8(Suppl 1):P61.
Results PGD2 increased in a dose-dependent manner IL-1induced COX-2 protein and mRNA expression. DP1 and CRTH2 were expressed and functional in chondrocytes. The effect of PGD2 was mimicked by DK-PGD2 and Indomethacin, selective agonists of CRTH2, but not by BW245C, a selective agonist of DP1. Furthermore, treatment with an anti-CRTH2 antibody reversed the effect of PGD2, indicating that the stimulatory effect of PGD2 is mediated by CRTH2. Activation of CRTH2 is consistent with the activation of a receptor coupled to a phosphoinositide-specific phospholipase, suggesting that the effect of PGD2 is mediated by the CRTH2/PIP2/PKC.
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Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center (CR-CHUM), Notre-Dame Hospital, Montreal, Quebec, Canada
© 2010 Zayed et al; licensee BioMed Central Ltd.
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