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The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells.

Li L, Fox B, Keeble J, Salto-Tellez M, Winyard PG, Wood ME, Moore PK, Whiteman M - J. Cell. Mol. Med. (2013)

Bottom Line: We have now assessed the effect of GYY4137 (a slow-releasing H2 S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro.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.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Science Research Division, King's College London, London, England.

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Related in: MedlinePlus

Effect of GYY4137 on LPS- and cytokine-induced synthesis of pro-inflammatory mediators in human articular chondrocytes (HAC). HAC were treated with GYY4137 at the concentrations stated for 1 or 5 hrs post-LPS (10 μg/ml) stimulation for 18 hrs. After this time, cell culture media were collected and analysed for (A) PGE2, (B) TNF-α and (C) IL-6 by commercial ELISA and (D) •NO (measured as NO2−) determined by Griess assay. Inhibitors of COX-2 (NS-398; 10 μM) and iNOS (1400W, 100 μM) were added for 1 hr prior to LPS stimulation. Data shown are mean ± SEM of at least three separate experiments. *P < 0.05 c.f. LPS-stimulated cells.
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fig02: Effect of GYY4137 on LPS- and cytokine-induced synthesis of pro-inflammatory mediators in human articular chondrocytes (HAC). HAC were treated with GYY4137 at the concentrations stated for 1 or 5 hrs post-LPS (10 μg/ml) stimulation for 18 hrs. After this time, cell culture media were collected and analysed for (A) PGE2, (B) TNF-α and (C) IL-6 by commercial ELISA and (D) •NO (measured as NO2−) determined by Griess assay. Inhibitors of COX-2 (NS-398; 10 μM) and iNOS (1400W, 100 μM) were added for 1 hr prior to LPS stimulation. Data shown are mean ± SEM of at least three separate experiments. *P < 0.05 c.f. LPS-stimulated cells.

Mentions: Treatment of HFLS (Fig. 1) or HAC (Fig. 2) with LPS significantly increased the levels of PGE2 [A], TNF-α [B], IL-6 [C] and •NO (measured as NO2−) [D] in culture supernatant of both joint cell types. Treatment of HFLS (Fig. 1A–D) or HAC (Fig. 2A–D) with GYY4137 (100–500 μM) for 1 hr prior to stimulation significantly reduced the levels of pro-inflammatory mediators in culture supernatant. Similarly, GYY4137 (>100 μM) significantly inhibited the increase in •NO (Fig. 1E) and PGE2 (Fig. 1F) levels induced by a cocktail of TNF-α (10 ng/ml), interleukin-1 beta (IL-1β; 1 ng/ml) and interferon-gamma (IFN-γ; 10 ng/ml).


The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells.

Li L, Fox B, Keeble J, Salto-Tellez M, Winyard PG, Wood ME, Moore PK, Whiteman M - J. Cell. Mol. Med. (2013)

Effect of GYY4137 on LPS- and cytokine-induced synthesis of pro-inflammatory mediators in human articular chondrocytes (HAC). HAC were treated with GYY4137 at the concentrations stated for 1 or 5 hrs post-LPS (10 μg/ml) stimulation for 18 hrs. After this time, cell culture media were collected and analysed for (A) PGE2, (B) TNF-α and (C) IL-6 by commercial ELISA and (D) •NO (measured as NO2−) determined by Griess assay. Inhibitors of COX-2 (NS-398; 10 μM) and iNOS (1400W, 100 μM) were added for 1 hr prior to LPS stimulation. Data shown are mean ± SEM of at least three separate experiments. *P < 0.05 c.f. LPS-stimulated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3823018&req=5

fig02: Effect of GYY4137 on LPS- and cytokine-induced synthesis of pro-inflammatory mediators in human articular chondrocytes (HAC). HAC were treated with GYY4137 at the concentrations stated for 1 or 5 hrs post-LPS (10 μg/ml) stimulation for 18 hrs. After this time, cell culture media were collected and analysed for (A) PGE2, (B) TNF-α and (C) IL-6 by commercial ELISA and (D) •NO (measured as NO2−) determined by Griess assay. Inhibitors of COX-2 (NS-398; 10 μM) and iNOS (1400W, 100 μM) were added for 1 hr prior to LPS stimulation. Data shown are mean ± SEM of at least three separate experiments. *P < 0.05 c.f. LPS-stimulated cells.
Mentions: Treatment of HFLS (Fig. 1) or HAC (Fig. 2) with LPS significantly increased the levels of PGE2 [A], TNF-α [B], IL-6 [C] and •NO (measured as NO2−) [D] in culture supernatant of both joint cell types. Treatment of HFLS (Fig. 1A–D) or HAC (Fig. 2A–D) with GYY4137 (100–500 μM) for 1 hr prior to stimulation significantly reduced the levels of pro-inflammatory mediators in culture supernatant. Similarly, GYY4137 (>100 μM) significantly inhibited the increase in •NO (Fig. 1E) and PGE2 (Fig. 1F) levels induced by a cocktail of TNF-α (10 ng/ml), interleukin-1 beta (IL-1β; 1 ng/ml) and interferon-gamma (IFN-γ; 10 ng/ml).

Bottom Line: We have now assessed the effect of GYY4137 (a slow-releasing H2 S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro.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.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Science Research Division, King's College London, London, England.

Show MeSH
Related in: MedlinePlus