6-Gingerol attenuates macrophages pyroptosis via the inhibition of MAPK signaling pathways and predicts a good prognosis in sepsis.
Cytokine
; 125: 154854, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31539844
ABSTRACT
BACKGROUND:
Sepsis is a major cause of death for ICU patients. Sepsis development depends heavily on the presence of mature IL-1ß cytokine. This study evaluates the potential therapeutic properties of a bioactive compound known as 6-gingerol on sepsis. This compound has previously been demonstrated to possess anti-inflammatory properties both in vivo and in vitro.METHODS:
C57BL/6 mice was used to establish models of sepsis by means of cecal ligation and puncture (CLP). Upon treatment with 6-gingerol, we assessed the survival rate of mice and measured the levels of key pro-inflammatory cytokines in serum and colon tissues. Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). The impact of 6-gingerol on pyroptosis was also examined. In addition, we assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and RAW264.7 cells.RESULTS:
In CLP mice, 6-gingerol significantly ameliorated sepsis development, which was associated with the reduction of serum IL-1ß. In BMDMs and RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release of caspase-1p20, HMGB1, mature IL-1ß, IL-18 in response to ATP and LPS treatment. 6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and caspase-1p20 release.CONCLUSIONS:
By targeting MAPK signaling, 6-gingerol significantly suppressed secretion of pro-inflammatory cytokines and inhibited macrophage cells pyroptosis resulting in overall inhibition of sepsis development.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Catecoles
/
Citocinas
/
Sepsis
/
Alcoholes Grasos
/
Piroptosis
/
Macrófagos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Cytokine
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China