Characterization of LITAF-deficient animals
Date
2007
DOI
Authors
Wong, Hsin-Tzu
Version
OA Version
Citation
Abstract
TNF-[alpha], an important cytokine mediator of immune regulation and inflammation, can harbor beneficial and detrimental properties through its proinflammatory and
proapoptotic effects in various cell types. It is regulated by transcription factors such as NFkB, ETS, and cAMP. Given the detrimental effects of TNF overproduction, TNF gene expression must be tightly regulated.
We identified a transcription factor named LITAF for LPS-Induced TNF AIpha Factor that regulates TNF-[alpha] transcription.This LITAF gene is located on the short (p) arm of chromosome 16 between positions 13.3 and 12. Our preliminary data indicate that blocking LITAF expression in THP-l macrophages results in the inhibition of LPS-induced TNF gene expression. These in vitro findings support our belief that, (1) LITAF is major regulator of TNF expression in vivo; (2) LITAF plays an important role in inflammatory disease.
The aims of the present study were to generate a homozygous mouse lacking the LITAF gene and use this model to assess the role of LITAF in inflammatory responses.
We generated a LITAF knockout mouse by heteroIogous recombination lacking either 1 LITAF allele: Heterozygous mouse; or both the LITAF alleles: Homozygous mouse by breeding heterozygous mice. With the generation of LITAF -/-mice, in vitro studies conducted to determine the contribution of LITAF to TNF expression in vivo; and to understand the role of LITAF in the inflammatory diseases.
Macrophages of eight LITAF -/- mice and eight wild type mice were extracted and challenged with E. coli LPS. TNF-a level of both groups were quantified at 4 hours and 24 hours after stimulation of LPS. Our results demonstrated that at both time point, TNF- [alpha] production of LITAF +/+ mice was 2.17 times more than that of LITAF
-/- macrophages.
Conclusion: LITAF-deficient animals exhibited decreased level of TNF-[alpha] production, that is approximately half of that of wild type animals. Therefore, our study confirms the importance of the role of LITAF, a transcriptional factor, in LPS induced TNF-[alpha] levels.
Description
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Thesis (MSD)--Boston University, Henry M. Goldman School of Dental Medicine, 2007 (Dept. of Periodontology and Oral Biology).
Includes bibliographical references: leaves 50-58.
Thesis (MSD)--Boston University, Henry M. Goldman School of Dental Medicine, 2007 (Dept. of Periodontology and Oral Biology).
Includes bibliographical references: leaves 50-58.
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.