title: The impact of P2X7 receptor antagonist, brilliant blue G on graft-versus-host disease in mice after allogeneic hematopoietic stem cell transplantation.
abstract: The purpose of this study was to investigate the role of P2X7 on liver inflammation in mice after HSCT. Hematopoietic stem cells obtained from C57BL/6 mice were administrated into BALB/c mice to establish GVHD model. On day 7, 14, 21 and 28 after HSCT, mice received P2X7R antagonist brilliant blue G (BBG) or not were sacrificed for analysis of weight loss, liver inflammation, cytokine secretion, P2X7, NLRP3 expression as well as caspase-1 activation. Liver inflammation with neutrophils and macrophases infiltration as well as weight loss increase was present after HSCT, but improved after administration with high dose of BBG compared with lower dose. High dose of P2X7R inhibitor administration after HSCT previously reduced levels of IL-1β, IL-18, caspase-1, NLRP3 as well as P2X7, and the level of alanine transaminase (ALT) and the ratio of aspartate amino transferase (AST)/ALT compared with that receiving low dose of BBG. Meanwhile, P2X7R blockage also reduced infiltration of macrophages and neutrophils and levels of CXCL8 and CCL2 in peripheral blood as well as improved liver function. In conclusion, blockage of P2X7R by BBG exerts a protective effect on GVHD post HSCT and improves liver function suggesting that this receptor could be considered as an attractive target for treatment of GVHD.
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou 221002, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou 221002, PR China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou 221002, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou 221002, PR China.
authors.forename: Shengyun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou 221002, PR China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China. Electronic address: cxf607001@163.com.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.affiliation: The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, PR China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou 221002, PR China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D043384:Glutamyl Aminopeptidase / Q000097:blood; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D012394:Rosaniline Dyes / Q000494:pharmacology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; D000410:Alanine Transaminase; D043384:Glutamyl Aminopeptidase; C004692:coomassie Brilliant Blue
keywords: Brilliant blue G; GVHD; Hematopoietic stem cell transplantation; P2X7R