Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells.
The purpose of this study was to identify the effect of sildenafil citrate on IL-1beta-induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1? stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1beta-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-1beta 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-1beta-induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1?-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.
Kim
Kyung-Ok
KO
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, New York 14642, USA.
Park
Shin-Young
SY
Han
Chang-Woo
CW
Chung
Hyun Kee
HK
Yoo
Dae-Hyun
DH
Ryu
Dae-Hyun
DH
Han
Joong-Soo
JS
D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000276:immunology / Q000494:pharmacology*; D010879:Piperazines / Q000276:immunology / Q000494:pharmacology*; D011687:Purines / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000276:immunology / Q000494:pharmacology*; D013583:Synovial Membrane / Q000201:enzymology / Q000276:immunology
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D006152:Cyclic GMP