Volume 8 Supplement 1

5th European Workshop on Immune-Mediated Inflammatory Diseases

Open Access

Valproic acid suppresses interleukin-1β-induced microsomal prostaglandin E2 Synthase-1 expression in chondrocytes

  • N Zayed1,
  • N Chabane1,
  • J Martel-Pelletier1,
  • J P Pelletier1,
  • N Duval1 and
  • H Fahmi1
Journal of Translational Medicine20108(Suppl 1):P60

https://doi.org/10.1186/1479-5876-8-S1-P60

Published: 25 November 2010

Introduction

Microsomal prostaglandin E2 Synthase (mPGES)-1 catalyzes the terminal step in the biosynthesis of PGE2. Early growth response factor-1 (Egr-1) is a key transcription factor in the regulation of mPGES-1. In the present study we examined the effects of valproic acid (VA), a histone deacetylase (HDAC) inhibitor, on interleukin (IL)-1β-induced mPGES-1-expression in human chondrocytes.

Methods

Chondrocytes were stimulated with IL-1 in the absence or presence of VA, and the level of mPGES-1 protein and mRNA expression were evaluated using Western blotting and real-time reverse-transcription polymerase chain reaction, respectively. The mPGES-1 promoter activity was analyzed in transient transfection experiments. Egr-1 recruitment to the mPGES-1 promoter were evaluated using chromatin immunoprecipitation (ChIP) assays.

Results

VA dose-dependently suppressed IL-1β-induced mPGES-1 protein and mRNA expression as well as its promoter activation. Treatment with VA did not alter IL-1-induced Egr-1 expression, nor its recruitment to the mPGES-1 promoter, but prevented its transcriptional activity.

Conclusion

Our study demonstrates that VA inhibits IL-1-induced mPGES-1 expression in chondrocytes. The suppressive effect of VA was not due to reduced expression or recruitment of Egr-1 to the mPGES-1 promoter.

Authors’ Affiliations

(1)
Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center (CR-CHUM), Notre-Dame Hospital, and Dept. of Medicine, University of Montreal

Copyright

© Zayed et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

Advertisement