title: Induction of BAFF expression by IFN-γ via JAK/STAT signaling pathways in human intestinal epithelial cells.
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.
authors.affiliation: DRI, and BK21 Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul, Korea.
authors.forename: Sun-Je
authors.initials: SJ
authors.lastname: Woo
authors.forename: Jintaek
authors.initials: J
authors.lastname: Im
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jeon
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Eun-Yi
authors.initials: EY
authors.lastname: Moon
authors.forename: Man Ki
authors.initials: MK
authors.lastname: Song
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D053612:Janus Kinases / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D020218:Response Elements / Q000235:genetics / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; C573415:IFNG protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C505719:TNFSF13B protein, human; D007371:Interferon-gamma; D053612:Janus Kinases