NYMC Faculty Publications
p53 Peptide Prevents LITAF-Induced TNF-Alpha-Mediated Mouse Lung Lesions and Endotoxic Shock
Author Type(s)
Faculty
Additional Author Affiliation
Touro College of Dental Medicine at NYMC
DOI
10.2174/156652411796268731
Journal Title
Current Molecular Medicine
First Page
439
Last Page
452
Document Type
Article
Publication Date
8-1-2011
Department
Pharmacology
Keywords
Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Down-Regulation, Gene Expression Regulation, Humans, Inflammation, Lipopolysaccharides, Lung, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Nuclear Proteins, Peptide Fragments, Promoter Regions, Genetic, Shock, Septic, Transcription Factors, Transfection, Tumor Necrosis Factor-alpha, Tumor Suppressor Protein p53
Disciplines
Medicine and Health Sciences
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.
Recommended Citation
Tang, X., O'Reilly, A., Asano, M., Merrill, J., Yokoyama, K., & Amar, S. (2011). p53 Peptide Prevents LITAF-Induced TNF-Alpha-Mediated Mouse Lung Lesions and Endotoxic Shock. Current Molecular Medicine, 11 (6), 439-452. https://doi.org/10.2174/156652411796268731
