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Prostaglandin E2 receptors EP1 and EP4 are up-regulated in rabbit chondrocytes by IL-1β, but not by TNFα

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Abstract

Prostaglandin E2 (PGE2) exerts its actions through the binding of the high affinity EP receptors. We wanted to evaluate the regulation of EP1 and EP4, and the expression of cyclooxigenase (COX)-2, main enzyme responsible for PGE2 synthesis in inflammatory situations, in healthy rabbit chondrocytes stimulated with inflammatory mediators locally increased during osteoarthritis. Articular chondrocytes obtained from healthy rabbits were stimulated with interleukin (IL)-1β (0.1–100 u/ml) or tumour necrosis factor (TNF)α (100 ng/ml). Where indicated, cells were preincubated with non-steroidal antiinflammatory drugs (NSAIDs) (10−6 M) to inhibit PGE2 synthesis. IL-1β induced a dose and time-dependent increase in EP1, EP4 and COX-2 expression. However, TNFα presence did not induce a significant modification in EP1, EP4 or COX-2 gene expression at any time of study. NSAID presence significantly inhibited PGE2 release but did not modify the EP receptors or COX-2 expression induced by IL-1β. Our results indicate that EP1 and EP4 receptors, and COX-2 are up-regulated in IL-1β-stimulated chondrocytes, while no significant modifications are observed in TNFα-stimulated cells. NSAIDs were unable to modify the expression of these mediators induced by IL-1β. Therefore, the increase in PGE2 synthesis, induced by IL-1β, does not seem to mediate the increase in EP receptor expression, in rabbit chondrocytes.

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Acknowledgments

This work was partially supported by research grants from the Spanish Ministry of Education (SAF2003/08379; SAF2006/2704) and Fondo de Investigaciones Sanitarias (CP03/00011; PI06/0032).

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Authors and Affiliations

  1. Joint and Bone Research Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain

    M. Angeles Alvarez-Soria, Raquel Largo, Olga Sanchez-Pernaute, Emilio Calvo, Jesús Egido & Gabriel Herrero-Beaumont

  2. Rheumatology Department, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040, Madrid, Spain

    Gabriel Herrero-Beaumont

Authors
  1. M. Angeles Alvarez-Soria
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  2. Raquel Largo
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  3. Olga Sanchez-Pernaute
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  4. Emilio Calvo
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  6. Gabriel Herrero-Beaumont
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Correspondence to Gabriel Herrero-Beaumont.

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Alvarez-Soria, M.A., Largo, R., Sanchez-Pernaute, O. et al. Prostaglandin E2 receptors EP1 and EP4 are up-regulated in rabbit chondrocytes by IL-1β, but not by TNFα. Rheumatol Int 27, 911–917 (2007). https://doi.org/10.1007/s00296-007-0328-3

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  • DOI: https://doi.org/10.1007/s00296-007-0328-3

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