title: Neoagarooligosaccharides prevent septic shock by modulating A20-and cyclooxygenase-2-mediated interleukin-10 secretion in a septic-shock mouse model.
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.
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Da Rae
authors.initials: DR
authors.lastname: Kang
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Gun Young
authors.initials: GY
authors.lastname: Yoon
authors.affiliation: Department of Neurosurgery, Konkuk University Hospital, Seoul 05030, South Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Hee Jo
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University, College of Medicine, Anam-dong, Sungbuk-Gu, Seoul 136-705, South Korea.
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Yoon
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea. Electronic address: immun3023@kku.ac.kr.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 380-701, South Korea. Electronic address: jungid@kku.ac.kr.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
mesh_terms: D000362:Agar / Q000737:chemistry; D000818:Animals; D051546:Cyclooxygenase 2 / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000737:chemistry; D012772:Shock, Septic / Q000276:immunology* / Q000517:prevention & control*; D016896:Treatment Outcome; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D009844:Oligosaccharides; D016753:Interleukin-10; D000362:Agar; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C513261:Tnfaip3 protein, mouse
keywords: A20; COX-2; IL-10; Neoagarooligosaccharides; Prevention; Sepsis