The effects of Twist-2 on liver endotoxin tolerance induced by a low dose of lipopolysaccharide.
Inflammation
; 37(1): 55-64, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24005898
ABSTRACT
Endotoxin tolerance is an important mechanism for preventing uncontrolled inflammatory cytokine production in bacterial sepsis. However, its molecular mechanisms remain largely unknown. It was reported that Twist-2 protein was a negative regulator for cytokine signaling by repressing the nuclear factor (NF)-κB-dependent cytokine pathway. However, the relationship between Twist-2 and endotoxin tolerance is unclear. Endotoxin tolerance models of BABL/c mice and isolated Kupffer cells (KCs) were established to observe the changes of Twist-2 during endotoxin tolerance. Then, Twist-2 shRNA was used to specifically inhibit Twist-2 gene in KCs to further explore the role of Twist-2 in endotoxin tolerance. The expression of Twist-2 was analyzed by immunohistochemistry, reverse transcription polymerase chain reaction, and Western blotting, respectively. The responses to lipopolysaccharide were assessed by the activation of nuclear factor-κB and the production of tumor necrosis factor-α. The histopathologic changes in the liver of the non-endotoxin tolerance group were more serious than those of the endotoxin tolerance group. Endotoxin tolerance also led to less activation of nuclear factor-κB, lower expression levels of tumor necrosis factor-α mRNA, and more expression of Twist-2 than those of non-endotoxin tolerance group in liver and KCs. Moreover, the inhibitive effects partly weaken in KCs transfected with Twist-2 shRNA. Twist-2 was involved in endotoxin tolerance through inhibiting NF-κB trans-activation and cytokines transcriptional activities. It may be a new target for the clinical treatment of sepsis and other inflammatory diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Lipopolissacarídeos
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Proteína 1 Relacionada a Twist
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Fator de Transcrição RelA
/
Células de Kupffer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Inflammation
Ano de publicação:
2014
Tipo de documento:
Article