Year: 2016
Type: dissertation
Abstract: E26 transformation-specific (Ets) transcription factors are key regulators of hematopoiesis, tissue differentiation, and development, characterized by the presence of evolutionarily conserved DNA-binding domain (DBD) which recognizes a core 5’-GGAA/T-3’ sequence in promoter and enhancer regions of target genes. Epithelium-specific Ets transcription factor-1 (ESE-1), or E74-like factor 3 (Elf3) in mice, is a member of the Ets protein family which is known to be constitutively expressed in epithelial tissues. However, ESE-1 is highly and rapidly induced in non-epithelial cells such as endothelial cells, macrophages, and fibroblasts by pro-inflammatory cytokines, despite its lack of expression under resting conditions in these cell types. ESE-1 is also prominently expressed in various human inflammatory diseases including rheumatoid arthritis and vasculitis, and is known to regulate important genes involved in inflammation such as cyclooxygenase-2 (COX-2). Therefore, previous studies have focused on identifying the role of ESE-1 in inflammation using various cell lines and transfection tools as well as an ESE-1 knockout mouse model, which led to discovery of its many target genes and transcriptional regulation by nuclear factor kappa B (NF-B), the central regulator of inflammation. To further enhance our understanding of ESE-1 in human inflammatory diseases, we hereby investigated the ESE-1 expression and function in human primary cells derived from patients suffering from sepsis or rheumatoid arthritis. We discovered that ESE-1 is constitutively expressed human neutrophils and overexpressed in those from septic patients, and that human and mouse neutrophils display distinct expression pattern of ESE-1/Elf3. Additionally, in contrast to earlier studies, we found that ESE-1 acts as a negative regulator of COX-2 in human rheumatoid arthritis synovial fibroblasts (RASFs). These findings, using new experimental approaches that take advantage of the increased availability of better analysis tools, provide new insights into the involvement of ESE-1 in human inflammatory diseases which were previously unrecognized.
Source: TSpace (University of Toronto)
Author: Chan Mi Lee
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2625038288