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Neoagarooligosaccharides prevent septic shock by modulating A20-and cyclooxygenase-2-mediated interleukin-10
Da Rae Kang1, Gun Young Yoon1, Joon Cho2
1Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
Abstract:
Analysis of the signaling mechanism triggered by endotoxin-mediated toll-like receptor-4 activation using immune cell systems or rodent models may help identify potential agents for the prevention of Gram-negative bacteria infection. β-agarase cleaves the β-1,4-linkages of agar to produce neoagarooligosaccharides (NAOs), which have various physiological functions. The aim of this study was to investigate the efficacy of NAOs in preventing experimental sepsis caused by the administration of endotoxin or Gram-negative bacteria. Organ damage and neutrophil infiltration in an endotoxemia and septic-shock mouse model were suppressed by NAOs. Pro-inflammatory cytokine level was decreased, but IL-10 level was increased by NAO-treatment. Further induction by NAOs in the presence of endotoxin was associated with a significant induction of A20 and cyclooxygenase (COX)-2 expressions. Our data suggest that NAOs have a beneficial preventive effect in septic shock correlated with the enhancement of IL-10 via the induction of A20 and COX-2.