Date of Award
Health Sciences (M.H.S.)
Jun/Fos and Jun/BATF heterodimers are capable of binding the TRE site to regulate gene transcription, which in turn amongst other functions, could be involved in the regulation of inflammation. Studies have shown that in contrast to Jun/Fos, the Jun/BATF heterodimers result in a reduced transcriptional activity and thus inhibit the expression of AP-1 target genes. The inflammatory response is composed of a vast array of mediators, including cytokines such as IL6 and IL10. The balance between pro-inflammatory and anti-inflammatory mediators, in part, determines whether the inflammatory response persists or is resolved. Macrophages are a key cell type involved in the inflammatory response.
The goal of this research was to determine the expression of BATF in comparison to Fos expression when M1 cells were stimulated with the known inflammatory triggers, IL6, IL10 and LPS. Although M1 cells do not express c-Fos, they do express Fra-1, which is also a member of the Fos family.
Stimulation of M1 cells with IL6, IL10 and LPS resulted in co-expression of BATF and Fra-1 as a result of stimulation with each inflammatory trigger. Further studies will be required to measure transcription factor binding to an AP-1 consensus DNA sequence. This would give more conclusive evidence as to which of the two dimers Jun/BATF or Jun/Fos is actually binding and thus giving rise to the control of the TRE site following the stimulations. This would also show whether the transcription factor that was predominantly expressed produced its effect through the TRE site or whether on the contrary, BATF and Fra-1 were coexpressed and had different promoter targets.
Goto, Lyna, "Transcriptional Regulation of M1 Cells in Response to IL-6, IL-10 and LPS" (2010). Masters Theses. 661.