Induction of BAFF expression by IFN‐γ via JAK/STAT signaling pathways in human intestinal epithelial cells. Issue 3 (27th December 2012)

• Record Type: Journal Article
• Authors: Woo, Sun‐Je; Im, Jintaek; Jeon, Jun Ho; Kang, Seok‐Seong; Lee, Mi‐Hee; Yun, Cheol‐Heui; Moon, Eun‐Yi; Song, Man Ki; Kim, Hong‐Hee; Han, Seung Hyun
• Is Part Of: Journal of leukocyte biology. Volume 93:Issue 3(2013)
• Page Start: 363
• Page End: 368
• Publication Date: 2012-12-27
• Subjects: B‐cell activating factor -- Interferon‐gamma -- HT‐29; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0412210
• Languages: English
• ISSNs: 0741-5400

Abstract

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. Abstract : 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.