Suppressive action of resolvin D1 on the production and release of septic mediators in D-galactosamine‑sensitized endotoxin shock mice

Murakami,Taisuke; Suzuki,Kaori; Tamura,Hiroshi; Nagaoka,Isao

doi:10.3892/etm.2010.170

Suppressive action of resolvin D1 on the production and release of septic mediators in D-galactosamine‑sensitized endotoxin shock mice

Authors:
- Taisuke Murakami
- Kaori Suzuki
- Hiroshi Tamura
- Isao Nagaoka
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Affiliations: Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo, Japan, Seikagaku Biobusiness Corporation, Tokyo, Japan
Published online on: December 2, 2010 https://doi.org/10.3892/etm.2010.170
Pages: 57-61

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Abstract

Endotoxin/septic shock is a severe condition induced during serious infections with Gram-negative bacteria. To evaluate the therapeutic potential of resolvin D1 (RvD1), a novel pro-resolving molecule, on endotoxin/septic shock, we investigated the effect of RvD1 on the extracellular release of high mobility group box-1 (HMGB1), the production of inflammatory cytokines, the accumulation of peritoneal cells and hepatocyte apoptosis in vivo using a D-galactosamine (GalN)-sensitized mouse endotoxin shock model. Serum HMGB1 levels were markedly elevated after challenge with lipopolysaccharide (LPS)/D-GalN, and RvD1 administration significantly reduced HMGB1 levels. Furthermore, the serum levels of inflammatory cytokines, such as TNF-α, IL-6, IL-10 and macrophage chemotactic protein (MCP)-1 were elevated in the endotoxin shock model. Importantly, RvD1 administration slightly reduced the TNF-α, IL-6 and IL-10 levels, and further lowered MCP-1 levels. Moreover, RvD1 administration affected the peritoneal cell accumulation and decreased the neutrophil population. Finally, LPS/D-GalN injection induced apoptosis in the liver (mostly of hepatocytes), and RvD1 administration reduced the apoptosis of hepatocytes. These observations suggest that RvD1 may be a therapeutic agent for sepsis/endotoxin shock by exerting suppressive action on the release and production of septic mediators (HMGB1 and inflammatory cytokines), the accumulation of peritoneal cells and hepatic apoptosis.

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