p53 peptide prevents LITAF-induced TNF-alpha-mediated mouse lung lesions and endotoxic shock.

Abstract:

: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.

journal_name

Curr Mol Med

authors

Tang X,O'Reilly A,Asano M,Merrill JC,Yokoyama KK,Amar S

doi

10.2174/156652411796268731

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

439-52

issue

6

eissn

1566-5240

issn

1875-5666

pii

CMM # 117

journal_volume

11

pub_type

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