Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Interleukin-1-Induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression in Human OA Chondrocytes Is Associated with Histone H3K4 Methylation.
El-Mansouri3, Fatima Ezzahra, Chabane3, Nadir, Zayed3, Nadia, Martel-Pelletier2, Johanne, Pelletier1, Jean-Pierre, Fahmi3, Hassan
CHUM-Notre-Dame Hospital, Montreal, QC, Canada
CR-CHUM, Notre-Dame Hospital, Montreal, QC, Canada
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, Montreal, QC, Canada
Increased expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 plays a key role in the pathogenesis of osteoarthritis (OA). 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-1b (IL-1)-induced COX-2 and iNOS expression in human OA chondrocytes
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).
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.
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.
To cite this abstract, please use the following information:
El-Mansouri, Fatima Ezzahra, Chabane, Nadir, Zayed, Nadia, Martel-Pelletier, Johanne, Pelletier, Jean-Pierre, Fahmi, Hassan; Interleukin-1-Induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression in Human OA Chondrocytes Is Associated with Histone H3K4 Methylation. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1489