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

Sun Je Woo, Jintaek Im, Jun Ho Jeon, Seok Seong Kang, Mi Hee Lee, Cheol Heui Yun, Eun Yi Moon, Man Ki Song, Hong Hee Kim, Seung Hyun Han

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 γ750 to γ500 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 γ800 to γ601 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.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalJournal of Leukocyte Biology
Volume93
Issue number3
DOIs
StatePublished - 2013

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