title: Busulfan and cyclosphamide induce liver inflammation through NLRP3 activation in mice after hematopoietic stem cell transplantation.
abstract: 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-1β 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-1β 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.
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Chu
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Haina
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Kunming
authors.initials: K
authors.lastname: Qi
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002066:Busulfan / Q000633:toxicity; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D002066:Busulfan