Interleukin‐12 treatment down‐regulates STAT4 and induces apoptosis with increasing ROS production in human natural killer cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: negative‐;    feedback mechanism;    transcription factors;   

DOI  :  10.1189/jlb.1210674

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

NKcellsareprominentmediatorsoftheimmunomodulatingandantiangiogenicactivityofIL‐12.However,theeffectofprolongedIL‐12treatmentonNKcellsisunclear.Inthisstudy,weobservedthatIL‐12initiallyactivatesNKcells,butprolongedIL‐12treatmentspecificallydown‐regulatesIL‐12signalingandinducesNKcellapoptosisassociatedwithasignificantreductionincytolyticactivityandIFN‐γproductioninresponsetofurtherIL‐12stimulation.FurtherresultsdemonstratethatprolongedIL‐12stimulationofNKcellsspecificallydecreasesthelevelofactivatedSTAT4protein,acriticalIL‐12signalingcomponent,throughdecreasingSTAT4mRNAandproteinlevelsratherthaninducingSTAT4proteindegradation.IL‐12treatmentinducesNKcellactivationaswellaslevelsofROS,butprolongedIL‐12treatmentcausesROSaccumulation,whichinturn,resultsinthelossofΔψm,thereleaseofcytochromec,andtheactivationofcaspase‐3,resultinginNKcellapoptosis.ThesefindingsprovidenewinsightsintoIL‐12regulationinhumanNKcells,whereIL‐12initiallypromotesNKcellactivationbutsubsequentlylimitsthisresponsethroughanegative‐feedbackmechanism...

【 授权许可】

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