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10.1038/srep17828

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suck abstract from ncbi


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pmid26635145
      Sci+Rep 2015 ; 5 (ä): 17828
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  • Busulfan and cyclosphamide induce liver inflammation through NLRP3 activation in mice after hematopoietic stem cell transplantation #MMPMID26635145
  • Qiao J ; Huang Y ; Xia Y ; Chu P ; Yao H ; Xu L ; Qi K ; Liu Y ; Xu K ; Zeng L
  • Sci Rep 2015[Dec]; 5 (ä): 17828 PMID26635145 show ga
  • The aim of this study was to evaluate the role of NLRP3 inflammasome on BU/CY-induced liver inflammation in mice after HSCT. HSCT mice model was established through infusion of 5 × 10(6) bone marrow mononuclear cells after conditioned with BU/CY. On day 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of liver inflammation, cytokine secretion, NLRP3 expression and caspase-1 activation as well as release of ATP and high-mobility group protein B1 (HMGB1). Furthermore, NLRP3 selective inhibitor (BAY 11-7082) was administrated into mice after HSCT to evaluate its effects on liver inflammation. Severe liver inflammation and damage with elevated secretion of IL-1? and IL-18 were found in mice after HSCT. Meanwhile, elevated expressions of NLRP3 and caspase-1 activation in liver were found. In addition, increased release of ATP and HMGB1 were observed. Selective inhibition of NLRP3 decreased caspase-1 activation and secretion of IL-1? and IL-18. Furthermore, NLRP3 inhibition also reduced infiltration of macrophages and neutrophils and improved liver function. In conclusion, NLRP3 was involved in BU/CY-induced liver inflammation after HSCT and selectively inhibited it ameliorated liver inflammation and improved liver function, suggesting targeting NLRP3 might be a new approach in the prophylaxis of liver inflammation after HSCT.
  • |Adenosine Triphosphate/metabolism [MESH]
  • |Animals [MESH]
  • |Busulfan/toxicity [MESH]
  • |Carrier Proteins/*biosynthesis/genetics [MESH]
  • |Chemical and Drug Induced Liver Injury/*genetics/metabolism/pathology [MESH]
  • |Disease Models, Animal [MESH]
  • |HMGB1 Protein/biosynthesis/genetics [MESH]
  • |Hematopoietic Stem Cell Transplantation/*adverse effects [MESH]
  • |Humans [MESH]
  • |Inflammasomes/genetics/metabolism [MESH]
  • |Inflammation/chemically induced/*genetics/pathology [MESH]
  • |Liver/drug effects/injuries/*metabolism/pathology [MESH]
  • |Mice [MESH]
  • |NLR Family, Pyrin Domain-Containing 3 Protein [MESH]
  • |Reactive Oxygen Species/metabolism [MESH]


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