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.
Anzeige
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.
Open AccessThis 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.