Expression of the secretory leukoprotease inhibitor gene in epithelial cells.

Abstract

The secretory leukoprotease inhibitor (SLPI) gene codes for a 12-kD protein that within the lung protects the airway epithelium from neutrophil elastase. Screening of 228 alleles in 114 individuals for sequence differences by RNase protection of genomic DNA revealed no detectable polymorphisms in SLPI gene exons II-IV. SLPI gene expression in the lung was demonstrated by identifying SLPI mRNA transcripts in bronchial epithelial cells freshly isolated from normals. Cell lines derived from mucosal surfaces (HS-24 bronchial squamous cell carcinoma, HeLa cervical carcinoma) actively transcribe the SLPI gene and contain SLPI mRNA transcripts, while lung fibroblasts demonstrate no evidence of SLPI gene expression. SLPI mRNA transcripts appear to be relatively stable, with mRNA levels only mildly affected by inhibition of RNA synthesis. Chromatin DNA of HS-24 cells demonstrates two DNase I hypersensitivity sites within the 5' flanking region of exon I of the SLPI gene, whereas fibroblast chromatin has no DNase I accessible sites in the same region. Further analysis of the 5' flanking region demonstrated two contiguous transcription start sites, CAAT and TATA boxes, and several potential regions of known DNA binding proteins. Overall, the SLPI gene appears to be a relatively nonpolymorphic, stable gene that is constitutively expressed at specific tissue sites, but has the potential to be modulated at both the transcriptional and posttranscriptional levels.