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Interleukin-1-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in human OA chondrocytes is associated with histone H3K4 methylation

  • N Chabane
  • N Zayed
  • J Martel-Pelletier
  • J P Pelletier
  • H Fahmi
Open Access
Poster presentation
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Keywords

Nitric Oxide iNOS Expression Histone Methylation Methylthio H3K4 Methylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Objective

Increased expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 plays a key role in the pathogenesis of osteoarthritis (OA) disease. Methylation of lysine 4 on histone H3 (H3K4) was shown to be of fundamental importance in the regulation of gene expression. In the present study, we investigated the role of H3K4 methylation in interleukin-1β (IL-1)-induced COX-2 and iNOS expression in human OA chondrocytes.

Methods

Chondrocytes were stimulated with IL-1 for various time periods and the expression of iNOS and COX-2 mRNAs and proteins were evaluated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, respectively. H3K4 methylation at the iNOS and COX-2 promoters was evaluated using chromatin immunoprecipitation (ChIP) assays. The role of histone methylation was further evaluated using the methyltransferase inhibitor, 5’-deoxy-5’(methylthio) adenosine (MTA).

Results

IL-1 induced iNOS and COX-2 mRNA and protein in a dose- and time-dependent manner. The induction of iNOS and COX-2 expression by IL-1 was associated with H3K4 di- and trimethylation at the iNOS and COX-2 promoters, whereas the levels of H3K4 monomethylation remained unchanged. Treatment with MTA inhibited IL-1-induced H3K4 methylation as well as IL-1-induced iNOS and COX-2 expression.

Conclusion

These results indicate that H3K4 methylation contributes to IL-1-induced iNOS and COX-2 expression and suggest that this pathway could be a potential target for pharmacological intervention in the treatment of OA disease.

Copyright information

© Zayed et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • N Chabane
    • 1
  • N Zayed
    • 1
  • J Martel-Pelletier
    • 1
  • J P Pelletier
    • 1
  • H Fahmi
    • 1
  1. 1.Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM)Notre-Dame Hospital and Dept. of Medicine, University of Montreal, MontrealQuebecCanada

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