Exp Mol Med.
2008 Jun;40(3):286-293. 10.3858/emm.2008.40.3.286.
Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells
- Affiliations
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- 1Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea. jshan@hanyang.ac.kr
- 2Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, New York 14642, USA.
- 3Department of Orthopedic Surgery, College of Medicine, Hanyang University, Seoul 133-791, Korea.
- 4Department of Rheumatology, College of Medicine, Hanyang UniversitySeoul 133-791, Korea.
- KMID: 756330
- DOI: http://doi.org/10.3858/emm.2008.40.3.286
Abstract
- The purpose of this study was to identify the effect of sildenafil citrate on IL-1 beta induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1 beta stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1 beta -induced NO synthesis was inhibited by guanylate cyclase (GC) inhibitor, LY83583. When the cells were treated with 8-bromo-cGMP, a hydrolyzable analog of cGMP, NO synthesis was increased upto 5-fold without IL-1 beta treatment suggesting that cGMP is an essential component for increasing the NO synthesis. Synoviocytes and chondrocytes contain strong cGMP phosphodiesterase (PDE) activity, which has biochemical features of PDE5. When SW982 cells were pretreated with sildenafil citrate (Viagra), a PDE5 specific inhibitor, sildenafil citrate significantly inhibited IL-1 beta -induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1 beta -induced NO synthesis and iNOS expressions in human synovial sarcoma cells, and sildenafil citrate may be able to suppress an inflammatory reaction of synovium through inhibition of NO synthesis and iNOS expression by cytokines.
Keyword
MeSH Terms
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Anti-Inflammatory Agents/immunology/pharmacology
Cell Line, Tumor
Cyclic GMP/analogs & derivatives/immunology/metabolism
Cyclic Nucleotide Phosphodiesterases, Type 2/antagonists & inhibitors/metabolism
Humans
Interleukin-1beta/*metabolism
Male
Nitric Oxide/*biosynthesis/genetics/immunology
Nitric Oxide Synthase Type II/*biosynthesis/genetics/immunology
Phosphodiesterase Inhibitors/immunology/*pharmacology
Piperazines/immunology/*pharmacology
Purines/immunology/pharmacology
Signal Transduction/drug effects/genetics/immunology
Sulfones/immunology/*pharmacology
Synovial Membrane/enzymology/immunology
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