Our work indicates thai the Stat 1 transcription factor mediates the expression of a subset of interferon (IFN)-y-inducible genes (typified by ICAM-1 and IRF-1) in airway epithelial cells, and that this pathway is activated during viral or asthmatic airway inflammation. In both conditions. Stall activation (monitored by phosphorylation and nuclear translocation) is accompanied by increased Stall expression in the airway epithelium raising the possibility that Stall autoregulation serves as an amplification mechanism for Stal 1-dependent gene expression. Accordingly, we invesligated the basis for regulation of Slatl gene expression and ils possible role in conirolling Stall target genes in primary-culture airway epithelial cells. We found thai Stall protein and niRNA levels are increased by trealment wilh IFN-α and -γ(bul nol IL-6. IL10, or G-CSF) in a dose- and time-dependent manner and that the IFNinducible expression of Stall is accompanied by concomitani increases in transcriplional initiation rate of Ihe Stall gene as well as coordinate increases in Stall target genes ICAM-1 and IRF-1. Furthermore, IFN-γ-inducible expression of an ICAM-1 promoter construct with a critical Stall-binding sile can be augmemed by cp-transfeclion with a Slatl expression vector. In addition, experiments" with a Stat I-deficient cell line (U3A) that was stably complememed with either low or high levels of Stall indicate thai Ihe cellular level of Stall expression dictales the level of IFN-γ-inducible expression of endogenous IRF-1. Taken logelher. the results suggesl lhat, in addition to Stat 1 activation, the level of Stat 1 expression is also sensitive to IFN, and that Stall-dependent increases in Stall gene transcription may serve to amplify IFN-inducible gene expression by increasing the cylosolic pool of transcriplion factor substraic.

Original languageEnglish
Pages (from-to)A1387
JournalFASEB Journal
Issue number8
StatePublished - Dec 1 1998


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