A novel signaling pathway, p53/STAT6B/MAPK/LITAF, in inflammatory process
MetadataShow full item record
Previous studies identified a novel transcriptional factor named LPS-induced TNF alpha factor (LITAF), involved in the regulation of pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-[alpha]), in response to LPS stimulation. These cytokines play a crucial role in the initiation and maintenance of the inflammatory process, and the overproduction of these cytokines is extremely deleterious to the host, as evidenced by their role in a variety of human diseases: Periodontitis, Rheumatoid Arthritis, or Crohn's disease. To determine the signal transduction pathway(s) involved in LPS-induced macrophages, we investigated the mapping of the LITAF signaling pathway in the mouse, assuming that mouse LITAF would behave similarly to a human's, as judged by their substantial homology. All signal transduction candidates were cloned and transfected in peritoneal mouse macrophages and MusLITAF promoter activity and along with Western blotting were used as readout assays. In addition, to test if LITAF-dependent cytokines production, including TNF-[alpha], is also mediated by the sane candidates, Multiplex cytokine assay was performed. The MusLITAF promoter assays along with Multiplex cytokine assay disclosed that mouse MAPK or mouse STAT6B can significantly activate mouse LITAF gene expression, and regulate LITAF-dependent cytokine production including TNF-[alpha]. Changes in promoter activity were found similar at protein levels. Interestingly, this study noticed that MAPK-activated LITAF pathway can be specifically blocked by p53 accumulation. However, it was found that LITAF production mediated after overexpression of STAT6B does not seem to be affected by p53. The mapping of the LITAF signaling pathway in the mouse disclosed the involvement of p53, MAPK, and STAT6B. Further studies will elucidate the mechanism between p53/STAT6B/MAPK and LITAF in inflammatory processes to potentially develop phamacotherapeutic intervention.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact firstname.lastname@example.org.Thesis (MSD) --Boston University, Goldman School of Dental Medicine, 2009 (Department of Periodontology and Oral Biology).Includes bibliographic references: leaves 34-39.
RightsThis 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 email@example.com.