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

[摘要] BAFFplaysanimportantroleinthedevelopmentofBcells.Here,weinvestigatedtheeffectofIFN‐γonBAFFexpressioninhumanintestinalepithelialcells.IFN‐γinducedsolubleandmembrane‐boundBAFFproductioninadose‐andtime‐dependentmanner.IFN‐γ‐inducedBAFFreleasefrompolarizedintestinalepithelialcellswasobservedinapicalandbasolateralcompartments.JAKIinhibitorsuppressedIFN‐γ‐inducedBAFFexpression.Moreover,IFN‐γenhancedSTAT1phosphorylationandexpressionofIRF‐1.TransienttransfectionandreportergeneassayshowedthattheBAFFpromoterregionspanning−750to−500bpfromthetranslationinitiationsitewascrucialforIFN‐γ‐inducedBAFFexpression.NucleotidesequenceanalysisrevealedaGASelementinthepromoterregion.ChIPassayconfirmedtheenhancedbindingofphosphorylatedSTAT1totheBAFFpromoterregionat−800to−601bp.Furthermore,IFN‐γenhancedDNAbindingtoGASanditstranscriptionalactivation,asdeterminedbytheEMSAandreportergeneassay.Collectively,theseresultssuggestthatIFN‐γinducesBAFFexpressioninhumanintestinalepithelialcellsthroughJAK/STATsignalingpathwaysthatmightactivatetheGASandIRF‐1‐bindingelementintheBAFFpromoter...

[学科分类] 生理学

[关键词] B‐cell activating factor;Interferon‐gamma;HT‐29