Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells.
10.3858/emm.2008.40.3.286
- Author:
Kyung Ok KIM
1
;
Shin Young PARK
;
Chang Woo HAN
;
Hyun Kee CHUNG
;
Dae Hyun RYU
;
Joong Soo HAN
Author Information
1. Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea. jshan@hanyang.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cyclic nucleotide phosphodiesterases, type 5;
interleukin-1beta;
nitric oxide;
nitric oxide synthase type II;
sildenafil
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(3):286-293
- CountryRepublic of Korea
- Language:English
-
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.
