Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.
Clin Immunol
; 162: 84-90, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26639193
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-1ß, 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
/
Transplante de Células-Tronco Hematopoéticas
/
Caspase 1
/
Ativação Enzimática
/
Inibidores de Caspase
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article