Proinflammatory phenotype activation in macrophages (M phi s) after sepsis orchestrates an inflammatory response leading to multiple organ dysfunction. Trehalose preserves cell viability during exposure to a range of environmental stresses. We investigated whether trehalose may inhibit endotoxin-induced activation of the inflammatory phenotype in M phi s. Rat peritoneal M phi s were stimulated with 50 mu g/mL of Salmonella enteritidis lipopolysaccharide (LPS). Stimulated M phi s were coincubated with trehalose (25, 50, and 100 mmol), sucrose (100 mmol), or RPMI alone. Macrophages cultures were used for Western blot analysis of extracellular-regulated kinase, c-jun-N terminal kinase, and inducible nitric oxide synthase; interleukin (IL) 1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) gene expression by real-time reverse transcriptase-polymerase chain reaction, and supernatants for measuring the release of inflammatory cytokines and nitrite content. In vitro trehalose significantly blunted LPS-induced extracellular-regulated kinase (LPS 21 +/- 6 integrated intensity; LPS + trehalose 100 mmol 2 +/- 0.3 integrated intensity), c-jun-N terminal kinase (LPS 15 +/- 5 integrated intensity; LPS + trehalose 100 mmol 3.5 +/- 0.9 integrated intensity), and inducible nitric oxide synthase activation (LPS = 12 +/- 3 integrated intensity; LPS + trehalose 100 mmol = 1 +/- 0.09 integrated intensity), blunted IL-1 beta (LPS = 5 +/- 1.9 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.5 +/- 0.8 n-folds/beta-actin), IL-6 (LPS = 4 +/- 1.5 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.4 +/- 0.5 n-folds/beta-actin), and TNF-alpha (LPS = 4.2 +/- 1.6 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.1 +/- 0.7 n-folds/beta-actin) gene expression, and markedly reduced the release of inflammatory cytokines and nitrite content. Furthermore, in vivo trehalose prevented mortality in rats challenged with a lethal dose (20 mg/kg; LD90) of LPS (80% survival rate and 70% survival rate 24 and 72 h after LPS injection, respectively) and reduced serum TNF-alpha. Sucrose did not modified inflammatory phenotype in vitro nor in vivo protected against enclotoxin-induced mortality. Our study suggests that trehalose inhibits proinflammatory phenotype activation in M phi s and prevents enclotoxin-induced mortality.

The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in experimental septic shock / L., Minutoli; D., Altavilla; A., Bitto; F., Polito; E., Bellocco; G., Lagana; Giuliani, Daniela; T., Fiumara; S., Magazu; P., Ruggeri; Guarini, Salvatore; F., Squadrito. - In: SHOCK. - ISSN 1073-2322. - STAMPA. - 27:(2007), pp. 91-96.

The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in experimental septic shock

GIULIANI, Daniela;GUARINI, Salvatore;
2007-01-01

Abstract

Proinflammatory phenotype activation in macrophages (M phi s) after sepsis orchestrates an inflammatory response leading to multiple organ dysfunction. Trehalose preserves cell viability during exposure to a range of environmental stresses. We investigated whether trehalose may inhibit endotoxin-induced activation of the inflammatory phenotype in M phi s. Rat peritoneal M phi s were stimulated with 50 mu g/mL of Salmonella enteritidis lipopolysaccharide (LPS). Stimulated M phi s were coincubated with trehalose (25, 50, and 100 mmol), sucrose (100 mmol), or RPMI alone. Macrophages cultures were used for Western blot analysis of extracellular-regulated kinase, c-jun-N terminal kinase, and inducible nitric oxide synthase; interleukin (IL) 1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) gene expression by real-time reverse transcriptase-polymerase chain reaction, and supernatants for measuring the release of inflammatory cytokines and nitrite content. In vitro trehalose significantly blunted LPS-induced extracellular-regulated kinase (LPS 21 +/- 6 integrated intensity; LPS + trehalose 100 mmol 2 +/- 0.3 integrated intensity), c-jun-N terminal kinase (LPS 15 +/- 5 integrated intensity; LPS + trehalose 100 mmol 3.5 +/- 0.9 integrated intensity), and inducible nitric oxide synthase activation (LPS = 12 +/- 3 integrated intensity; LPS + trehalose 100 mmol = 1 +/- 0.09 integrated intensity), blunted IL-1 beta (LPS = 5 +/- 1.9 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.5 +/- 0.8 n-folds/beta-actin), IL-6 (LPS = 4 +/- 1.5 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.4 +/- 0.5 n-folds/beta-actin), and TNF-alpha (LPS = 4.2 +/- 1.6 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.1 +/- 0.7 n-folds/beta-actin) gene expression, and markedly reduced the release of inflammatory cytokines and nitrite content. Furthermore, in vivo trehalose prevented mortality in rats challenged with a lethal dose (20 mg/kg; LD90) of LPS (80% survival rate and 70% survival rate 24 and 72 h after LPS injection, respectively) and reduced serum TNF-alpha. Sucrose did not modified inflammatory phenotype in vitro nor in vivo protected against enclotoxin-induced mortality. Our study suggests that trehalose inhibits proinflammatory phenotype activation in M phi s and prevents enclotoxin-induced mortality.
27
91
96
The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in experimental septic shock / L., Minutoli; D., Altavilla; A., Bitto; F., Polito; E., Bellocco; G., Lagana; Giuliani, Daniela; T., Fiumara; S., Magazu; P., Ruggeri; Guarini, Salvatore; F., Squadrito. - In: SHOCK. - ISSN 1073-2322. - STAMPA. - 27:(2007), pp. 91-96.
L., Minutoli; D., Altavilla; A., Bitto; F., Polito; E., Bellocco; G., Lagana; Giuliani, Daniela; T., Fiumara; S., Magazu; P., Ruggeri; Guarini, Salvatore; F., Squadrito
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