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Clin Immunol. 2016 Jan;162:84-90. doi: 10.1016/j.clim.2015.11.012. Epub 2015 Nov 27.

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

Author information

1
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China; Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
2
Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
3
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
4
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China; Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. Electronic address: lihmd@163.com.
5
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China; Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China. Electronic address: zengly2000@163.com.

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.

KEYWORDS:

Bone marrow inflammation; Caspase-1; Hematopoietic stem cell transplantation; Inflammasomes

PMID:
26639193
DOI:
10.1016/j.clim.2015.11.012
[Indexed for MEDLINE]

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