期刊
FEBS OPEN BIO
卷 11, 期 6, 页码 1638-1644出版社
WILEY
DOI: 10.1002/2211-5463.13161
关键词
Caudal‐ related homeobox transcription factor 2; gene regulation; inflammatory bowel disease; interleukin‐ 33; intestinal regulation; transcriptional control
资金
- Independent Research Fund Denmark [4004-00140B]
- Lundbeck Foundation
- Fonden til Laegevidenskabens Fremme (the A. P. Moller Foundation)
- Foundation of Aase and Ejnar Danielsen, Laege Sofus Carl Emil Friis & Hustru Olga Doris Friis' Legat
- Region Zealand Foundation for Health and Research
- Danish National Research Foundation [DNRF107]
The study investigated whether CDX2 regulates IL33 mRNA expression, and found that CDX2 concentration-dependently upregulates IL33 expression.
Dysregulation of interleukin-33 (IL-33) has been implicated in the pathogenesis of several autoimmune and inflammatory diseases, but few studies have examined transcriptional regulation of the IL33 gene. In the intestines, gene regulation is controlled by a transcription factor network of which the intestinal-specific transcription factor CDX2 is a key component. In this study, we investigated whether CDX2 regulates IL33 mRNA expression. We examined IL33 mRNA expression in primary colonic epithelial cells from healthy humans and epithelial cell lines, revealing high expression levels in primary colonic and LS174T cells. Combining genomics data (ChIP-seq, RNA-seq) and IL33 promoter analyses in LS174T cells revealed intronic enhancer activity in the IL33 gene that is dependent on CDX2 expression. Western blotting and qRT-PCR confirmed that IL33 expression is upregulated in a CDX2 concentration-dependent manner, thereby providing the first evidence that CDX2 regulates the expression of IL33.
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