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Induction of BAFF expression by IFN-γ via JAK/STAT signaling pathways in human intestinal epithelial cells
- Source :
- Journal of Leukocyte Biology. 93:363-368
- Publication Year :
- 2012
- Publisher :
- Oxford University Press (OUP), 2012.
-
Abstract
- In human intestinal epithelial cells, IFN-γ induces BAFF expression through the signaling pathway of JAK/STAT and GAS, in the promoter region of the BAFF gene. BAFF plays an important role in the development of B cells. Here, we investigated the effect of IFN-γ on BAFF expression in human intestinal epithelial cells. IFN-γ induced soluble and membrane-bound BAFF production in a dose- and time-dependent manner. IFN-γ-induced BAFF release from polarized intestinal epithelial cells was observed in apical and basolateral compartments. JAK I inhibitor suppressed IFN-γ-induced BAFF expression. Moreover, IFN-γ enhanced STAT1 phosphorylation and expression of IRF-1. Transient transfection and reporter gene assay showed that the BAFF promoter region spanning −750 to −500 bp from the translation initiation site was crucial for IFN-γ-induced BAFF expression. Nucleotide sequence analysis revealed a GAS element in the promoter region. ChIP assay confirmed the enhanced binding of phosphorylated STAT1 to the BAFF promoter region at −800 to −601 bp. Furthermore, IFN-γ enhanced DNA binding to GAS and its transcriptional activation, as determined by the EMSA and reporter gene assay. Collectively, these results suggest that IFN-γ induces BAFF expression in human intestinal epithelial cells through JAK/STAT signaling pathways that might activate the GAS and IRF-1-binding element in the BAFF promoter.
- Subjects :
- Transcriptional Activation
Immunology
Response Elements
Cell Line
Interferon-gamma
stomatognathic system
Intestinal mucosa
immune system diseases
B-Cell Activating Factor
Humans
Immunology and Allergy
STAT1
Intestinal Mucosa
Phosphorylation
B-cell activating factor
Janus Kinases
Reporter gene
biology
Epithelial Cells
Promoter
Cell Biology
Molecular biology
stomatognathic diseases
STAT1 Transcription Factor
Cell culture
biology.protein
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 19383673 and 07415400
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Journal of Leukocyte Biology
- Accession number :
- edsair.doi.dedup.....a46601837687ad9cf5194cec86383b61