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Prostaglandin D2 enhances interleukin -1beta-induced cyclooxygenase-2 expression in osteoarthritic cartilage

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.

Results

PGD2 increased in a dose-dependent manner IL-1-induced 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.

Conclusion

PGD2 stimulates IL-1-induced production of COX-2 by chondrocytes through the CRTH2/PIP2/PKC signalling pathway.

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Correspondence to N Zayed.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zayed, N., El Mansouri, F.E., Chabane, N. et al. Prostaglandin D2 enhances interleukin -1beta-induced cyclooxygenase-2 expression in osteoarthritic cartilage. J Transl Med 8, P61 (2010). https://doi.org/10.1186/1479-5876-8-S1-P61

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Keywords

  • Signalling Pathway
  • mRNA Expression
  • Prostaglandin
  • Indomethacin
  • Selective Agonist