NYMC Faculty Publications
A Novel Lipopolysaccharide-Induced Transcription Factor Regulating Tumor Necrosis Factor Alpha Gene Expression: Molecular Cloning, Sequencing, Characterization, and Chromosomal Assignment
Author Type(s)
Faculty
Additional Author Affiliation
Touro College of Dental Medicine at NYMC
DOI
10.1073/pnas.96.8.4518
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
First Page
4518
Last Page
4523
Document Type
Article
Publication Date
4-13-1999
Department
Pharmacology
Abstract
Lipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. Given the deleterious effects to the host of TNF-alpha, it has been postulated that TNF-alpha gene expression must be tightly regulated. The nature of the nuclear factor(s) that control TNF-alpha gene transcription in humans remains obscure, although NF-kappaB has been suggested. Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from -550 to -487 in the human TNF-alpha promoter that contains transcriptional activity, but lacks any known NF-kappaB-binding sites. We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its amino-terminal sequence, which was used to design degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells; hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts. In addition, high level of expression of LITAF mRNA was observed predominantly in the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally, chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that LITAF plays an important role in the activation of the human TNF-alpha gene and proposes a new mechanism to control TNF-alpha gene expression.
Recommended Citation
Myokai, F., Takashiba, S., Lebo, R., & Amar, S. (1999). A Novel Lipopolysaccharide-Induced Transcription Factor Regulating Tumor Necrosis Factor Alpha Gene Expression: Molecular Cloning, Sequencing, Characterization, and Chromosomal Assignment. Proceedings of the National Academy of Sciences of the United States of America, 96 (8), 4518-4523. https://doi.org/10.1073/pnas.96.8.4518
