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p53 Peptide Prevents LITAF-Induced TNF-Alpha-Mediated Mouse Lung Lesions and Endotoxic Shock

[ Vol. 11 , Issue. 6 ]


X. Tang, A. O'Reilly, M. Asano, J. C. Merrill, K. K. Yokoyama and S. Amar   Pages 439 - 452 ( 14 )


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.


p53, regulation, TNF-α, inflammatory disease, gene expression, macrophages, immune system disorders, LITAF, Cell Culture, ELISA, DNA Constructs, Protein Purification, Western Blot Analysis, DNA Probe


Boston University, Goldman School of Dental Medicine, 650 Albany Street, X-343,Boston, MA 02118, USA.

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