Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation.

Abstract

Epithelial-specific ETS-1 (ESE1), also named as ELF3, ERT and ESX, belonging to the ETS family of transcription factors, exerts multiple activities in inflammation, epithelial differentiation and cancer development. Previous data demonstrated that ESE1 synergizes with NF-κB to induce inflammation and drive tumor progress, and the nuclear translocation of ESE1 promotes colon cells apoptosis. However, the expression and biological functions of ESE1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that ESE1/ELF3 was over-expressed in intestinal epithelial cells (IECs) of patients with UC. In DSS-induced colitis mouse models, we observed the up-regulation of ESE1/ELF3 accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and NF-κB activation indicators [phosphorylated NF-κB p65 subunit (p-p65) and p-IκB] in colitis IECs. Increased co-localization of ESE1/ELF3 with active caspase-3 (and p-p65) in IECs of the DSS-induced colitis group further indicated the possible involvement of ESE1/ELF3 in NF-κB-mediated IEC apoptosis in UC. Employing the TNF-α-treated HT-29 cells as an IEC apoptosis model, we confirmed the positive correlation of ESE1/ELF3 with NF-κB activation and caspase-dependent IEC apoptosis in vitro. Immunoprecipitation and immunofluorescence assay revealed the physical interaction and increased nuclear translocation of ESE1/ELF3 and the NF-κB p65 subunit in TNF-α-treated HT-29 cells. Knocking ESE1/ELF3 down by siRNA significantly alleviated TNF-α-induced NF-κB activation and cellular apoptosis in HT-29 cells. Taken together, our data suggested that ESE1/ELF3 may promote the UC progression via accelerating NF-κB activation and thus facilitating IEC apoptosis.

• Authors: Liren Li, Xianjing Miao, Runzhou Ni, Xiaobing Miao, Liang Wang, Xiaodan Gu, Lijun Yan, Qiyun Tang, Dongmei Zhang
• Journal: Immunologic research (Immunol Res) Vol. 62 Issue 2 Pg. 198-212 (Jun 2015) ISSN: 1559-0755 [Electronic] United States
• PMID: 25926267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• ELF3 protein, human
• NF-kappa B
• Proto-Oncogene Proteins c-ets
• Transcription Factors
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Apoptosis (genetics)
• Case-Control Studies
• Cell Line
• Colitis, Ulcerative (chemically induced, genetics, metabolism, pathology)
• DNA-Binding Proteins (genetics, metabolism)
• Disease Models, Animal
• Female
• Gene Expression
• HT29 Cells
• Humans
• Immunohistochemistry
• Intestinal Mucosa (metabolism, pathology)
• Mice
• NF-kappa B (metabolism)
• Protein Transport
• Proto-Oncogene Proteins c-ets (genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)