Induction of BAFF expression by IFN-γ via JAK/STAT signaling pathways in human intestinal epithelial cells

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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.
Funding Information
  • National Research Foundation (NRF) of Korea
  • Ministry of Education, Science, and Technology
  • MEST (R01-2008-000-20127-0, 2012-0008693, 2012-0000492)
  • R&D Convergence Center Support Program, Ministry for Food, Agriculture, Forestry and Fisheries

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