Fas Ligand Induction in Human NK Cells Is Regulated by Redox Through a Calcineurin-Nuclear Factors of Activated T Cell-Dependent Pathway

摘要: Fas ligand (FasL) on cytotoxic lymphocytes is important for mediating apoptosis of activated and other target cells. We have reported that NK cell functions, such as proliferation, death, killing activity, are subject to regulation by cellular redox status. Here, we report expression FasL protein mRNA in cells also regulated redox. Ligation CD16 IL-2-preactivated resulted reduction intracellular peroxide level well induction expression. This CD16-induced was suppressed oxidative stress, including thiol deprivation or treatment with hydrogen (H 2 O ). Addition thiol-reducing compounds, l-cystine, 2-ME, N -acetyl cysteine, restored These data suggest stimulation requires reducing status Because gene activation following cross-linking the NF T (NFAT), examined effect stresses NFAT activation. Electrophoretic mobility shift assays revealed both insufficiency H DNA-binding activity addition compounds reversed even enhanced it. Furthermore, these inhibited calcineurin, a serine/threonine phosphatase regulates results suppression calcineurin mechanism which stress inhibits further support hypothesis might be required maintenance optimal functions under physiologic conditions.