Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.

Abstract

Conditioning regimens before hematopoietic stem cell transplantation (HSCT), cause damage to bone marrow and inflammation. Whether inflammasomes are involved in bone marrow inflammation remains unclear. The study aims to evaluate the role of inflammasomes in bone marrow inflammation after HSCT. On days 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of bone marrow inflammation, pro-inflammatory cytokines secretion, inflammasomes expression and caspase-1 activation. Bone marrow inflammation with neutrophils and macrophages infiltration was observed after HSCT. Secretion of IL-1β, IL-18, TNF-α and IL-6 were elevated, with increased caspase-1 activation and inflammasomes expression. Caspase-1 inhibitor administration after HSCT significantly reduced infiltration of neutrophils and macrophages into bone marrow and increased the numbers of megakaryocytes and platelets. In conclusion, inflammasomes activation is involved in bone marrow inflammation after HSCT and caspase-1 inhibition attenuates bone marrow inflammation and promoted hematopoietic reconstitution, suggesting targeting caspase-1 might be beneficial for improving HSCT outcomes.

• Authors: Jianlin Qiao, Jinyan Wu, Yuanyuan Li, Yuan Xia, Peipei Chu, Kunming Qi, Zhiling Yan, Haina Yao, Yun Liu, Kailin Xu, Lingyu Zeng
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 162 Pg. 84-90 (Jan 2016) ISSN: 1521-7035 [Electronic] United States
• PMID: 26639193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Caspase Inhibitors
• Caspase 1

Topics

• Animals
• Bone Marrow (immunology)
• Caspase 1 (genetics, metabolism)
• Caspase Inhibitors (pharmacology)
• Down-Regulation
• Enzyme Activation (drug effects)
• Hematopoietic Stem Cell Transplantation
• Humans
• Inflammation (physiopathology)
• Mice