Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin.
Br J Pharmacol
; 180(8): 1132-1147, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36479683
ABSTRACT
BACKGROUND AND PURPOSE:
Intravenous infusion of chemotherapy drugs can cause severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear. EXPERIMENTALAPPROACH:
RNA-sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein-5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone-marrow-derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN-induced CIP in vivo. The anti-CIP effect of aescin was evaluated, both in vivo and in vivo. KEYRESULTS:
Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN-induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL-1ß. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis. CONCLUSION AND IMPLICATIONS These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flebite
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China