PMID- 26635145 OWN - NLM STAT- MEDLINE DCOM- 20161006 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 5 DP - 2015 Dec 4 TI - Busulfan and cyclosphamide induce liver inflammation through NLRP3 activation in mice after hematopoietic stem cell transplantation. PG - 17828 LID - 10.1038/srep17828 [doi] LID - 17828 AB - 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 x 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-1beta 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-1beta 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. FAU - Qiao, Jianlin AU - Qiao J AD - Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Huang, Yujin AU - Huang Y AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Xia, Yuan AU - Xia Y AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Chu, Peipei AU - Chu P AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Yao, Haina AU - Yao H AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Xu, Linyan AU - Xu L AD - Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Qi, Kunming AU - Qi K AD - Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. FAU - Liu, Yun AU - Liu Y AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Xu, Kailin AU - Xu K AD - Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. FAU - Zeng, Lingyu AU - Zeng L AD - Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. AD - Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151204 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Carrier Proteins) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - G1LN9045DK (Busulfan) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Busulfan/toxicity MH - Carrier Proteins/*biosynthesis/genetics MH - Chemical and Drug Induced Liver Injury/*genetics/metabolism/pathology MH - Disease Models, Animal MH - HMGB1 Protein/biosynthesis/genetics MH - Hematopoietic Stem Cell Transplantation/*adverse effects MH - Humans MH - Inflammasomes/genetics/metabolism MH - Inflammation/chemically induced/*genetics/pathology MH - Liver/drug effects/injuries/*metabolism/pathology MH - Mice MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - Reactive Oxygen Species/metabolism MH - Signal Transduction PMC - PMC4669461 EDAT- 2015/12/05 06:00 MHDA- 2016/10/08 06:00 PMCR- 2015/12/04 CRDT- 2015/12/05 06:00 PHST- 2015/06/10 00:00 [received] PHST- 2015/11/06 00:00 [accepted] PHST- 2015/12/05 06:00 [entrez] PHST- 2015/12/05 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] PHST- 2015/12/04 00:00 [pmc-release] AID - srep17828 [pii] AID - 10.1038/srep17828 [doi] PST - epublish SO - Sci Rep. 2015 Dec 4;5:17828. doi: 10.1038/srep17828.