The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages

Whiteman, M., Li, L., Rose, P. , Tan, C.-H., Parkinson, D. B. and Moore, P. K. (2010) The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages. Antioxidants and Redox Signaling, 12 (10). pp. 1147-1154. ISSN 1523-0864

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The role of hydrogen sulfide (H2S) in inflammation is controversial, with both pro- and antiinflammatory effects documented. Many studies have used simple sulfide salts as the source of H2S, which give a rapid bolus of H2S in aqueous solutions and thus do not accurately reflect the enzymatic generation of H2S. We therefore compared the effects of sodium hydrosulfide and a novel slow-releasing H 2S donor (GYY4137) on the release of pro- and antiinflammatory mediators in lipopolysaccharide (LPS)-treated murine RAW264.7 macrophages. For the first time, we show that GYY4137 significantly and concentration-dependently inhibits LPS-induced release of proinflammatory mediators such as IL-1β, IL-6, TNF-α, nitric oxide (�NO), and PGE2 but increased the synthesis of the antiinflammatory chemokine IL-10 through NF-κB/ATF-2/HSP-27-dependent pathways. In contrast, NaHS elicited a biphasic effect on proinflammatory mediators and, at high concentrations, increased the synthesis of IL-1β, IL-6, NO, PGE2 and TNF-α. This study clearly shows that the effects of H2S on the inflammatory process are complex and dependent not only on H2S concentration but also on the rate of H2S generation. This study may also explain some of the apparent discrepancies in the literature regarding the pro- versus antiinflammatory role of H2S. Antioxid. Redox Signal. 12, 1147-1154. © Copyright 2010, Mary Ann Liebert, Inc.

Keywords:activating transcription factor 2, gyy 4137, heat shock protein 27, hydrogen sulfide, immunoglobulin enhancer binding protein, interleukin 10, interleukin 1beta, interleukin 6, lipopolysaccharide, morpholine derivative, nitric oxide, prostaglandin E2, sodium hydrogen sulfide, sulfide, tumor necrosis factor alpha, unclassified drug, antiinflammatory activity, article, cell culture, concentration (parameters), cytokine production, enzyme synthesis, inflammation, macrophage, priority journal, Activating Transcription Factor 2, Air Pollutants, Animals, Cell Line, HSP27 Heat-Shock Proteins, Inflammation Mediators, Lipopolysaccharides, Macrophages, Mice, Morpholines, NF-kappa B, Organothiophosphorus Compounds, Sulfides, Murinae
Subjects:B Subjects allied to Medicine > B100 Anatomy, Physiology and Pathology
Divisions:College of Science > School of Life Sciences
ID Code:9799
Deposited On:10 Jun 2013 10:55

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