p53 peptide prevents LITAF-induced TNF-alpha-mediated mouse lung lesions and endotoxic shock.
Curr Mol Med
; 11(6): 439-52, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21663590
Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a transcription factor LPS-induced TNF factor (LITAF) significantly induces TNF-α production. Furthermore, we found that p53 and its synthetic peptide 162-motif specifically downregulate LITAF/TNF-α gene expression in human cells in vitro. Thus, in the present study, the role of p53 in regulating TNF-α-mediated inflammation was investigated. Our data showed that a synthetic peptide, named 162-motif, corresponding to this region functions independently from p53 to cause a significant suppression of TNF-α gene expression in mouse primary macrophages. The 162-motif, when delivered into cells and organs, reduces serum TNF-α level in mice and prevents TNF-α-induced lung lesions and endotoxic shock. Our findings highlight the regulation of LITAF/TNF-α by p53 and its short peptide 162-motif. These in vitro and in vivo observations serve to pave the way for pharmacotherapeutic approaches in the treatment of inflammatory diseases.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Choque Séptico
/
Factores de Transcripción
/
Proteínas Nucleares
/
Proteína p53 Supresora de Tumor
/
Factor de Necrosis Tumoral alfa
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos