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| Content Provider | PubMed Central |
|---|---|
| Author | Li, Ling Fox, Bridget Keeble, Julie Manuel, Salto-tellez Winyard, Paul G. Wood, Mark E. Moore, Philip K. Whiteman, Matthew |
| Copyright Year | 2013 |
| Abstract | The role of hydrogen sulfide (H2S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1–0.5 mM) decreased LPS-induced production of nitrite (NO2 −), PGE2, TNF-α and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-κB activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-α converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activity and decreased TNF-α, IL-1β, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration. |
| Related Links | http://dx.doi.org/10.1111/jcmm.12016 |
| Ending Page | 376 |
| Page Count | 12 |
| Starting Page | 365 |
| File Format | |
| ISSN | 15821838 |
| e-ISSN | 15824934 |
| Journal | Journal of Cellular and Molecular Medicine |
| Issue Number | 3 |
| Volume Number | 17 |
| Language | English |
| Publisher | Blackwell Publishing Ltd |
| Publisher Date | 2013-03-01 |
| Access Restriction | Open |
| Rights Holder | Blackwell Publishing Ltd |
| Subject Keyword | Molecular Medicine Cell Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Medicine |
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