4.8 Article

Class A CpG Oligonucleotide Priming Rescues Mice from Septic Shock via Activation of Platelet-Activating Factor Acetylhydrolase

Journal

FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01049

Keywords

Class A CpG oligodeoxynucleotide; sepsis; lipopolysaccharide; platelet-activating factor; plateletactivating factor acetylhydrolase; disseminated intravascular coagulation

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Funding

  1. [16J02224]
  2. [17H03907]
  3. Grants-in-Aid for Scientific Research [16J02224] Funding Source: KAKEN

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Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF) induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A(1585)) strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A(1585) rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation. Furthermore, CpG-A(1585) improved endotoxin shock induced by lipopolysaccharide, which comprises the cell wall of Gram-negative bacteria and inhibits inflammatory responses induced by cytokines such as interleukin-6 and tumor necrosis factor-alpha. These results suggest that CpG-A(1585) is a potential therapeutic target to prevent sepsis-related induction of PAF.

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