Molecular characterization of the mouse Fas ligand promoter in airway epithelial cells

Constitutively expressed Fas ligand in several distinct epithelial cell typ es appears to protect tissues by inducing apoptosis of Fas(+) immune cells during inflammatory reactions. To study the transcriptional regulation of F as ligand gene in airway epithelial cells, a 618-bp 5'-flanking region of m ouse Fas ligand gene was cloned, sequenced, and the transcriptional start s ite was determined by using 5'-RACE. Deletion analysis, gel mobility shift assays and site-directed mutagenesis indicated that a CCAAT box located -21 4 bp upstream from the transcription start site served as a major positive regulatory cis-element in an airway epithelial cell line. This element was not required for constitutive Fas ligand expression in Sertoli cells. Furth ermore, the activity of the site did not involve the NF-Y protein complex o r c/EBP protein family. UV-cross linking proteins to this element indicated that a similar to 23-kDa transcription factor bound to the Fas ligand prom oter CCAAT box and, thus, likely plays an important role in the regulation of Fas ligand expression in airway epithelial cells. (C) 2000 Elsevier Scie nce B.V. All rights reserved.