The impact of P2X7 receptor antagonist, brilliant blue G on graft-versus-host disease in mice after allogeneic hematopoietic stem cell transplantation

• Weight change of rat with GVHD decreased significantly after administration of BBG.
• Levels of P2X7, NLRP3, IL-1β, IL-18 and caspase-1 showed similar trend receiving BBG.
• The level of ALT and the ratio of AST/ALT were reduced after received 75 mg/kg BBG.
• Protein levels of CD68 and MPO were decreased in high dose group compared with lower.
• Levels of CXCL8 and CCL2 were reduced after administrated with high dose of BBG.

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.