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.
| Original language | English |
|---|---|
| Pages (from-to) | 2207-2215 |
| Number of pages | 9 |
| Journal | Journal of Clinical Investigation |
| Volume | 87 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1 Jan 1991 |
| Externally published | Yes |
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Keywords
- 5′ flanking region
- DNase I hypersensitivity site
- mRNA transcript stability
- Polymorphism
- Transcription
ASJC Scopus subject areas
- Medicine(all)
Cite this
Expression of the secretory leukoprotease inhibitor gene in epithelial cells. / Abe, Tatsuya; Kobayashi, Nobuyuki; Yoshimura, Kunihiko; Trapnell, Bruce C.; Kim, Haimee; Hubbard, Richard C.; Brewer, Michael T.; Thompson, Robert C.; Crystal, Ronald.
In: Journal of Clinical Investigation, Vol. 87, No. 6, 01.01.1991, p. 2207-2215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of the secretory leukoprotease inhibitor gene in epithelial cells
AU - Abe, Tatsuya
AU - Kobayashi, Nobuyuki
AU - Yoshimura, Kunihiko
AU - Trapnell, Bruce C.
AU - Kim, Haimee
AU - Hubbard, Richard C.
AU - Brewer, Michael T.
AU - Thompson, Robert C.
AU - Crystal, Ronald
PY - 1991/1/1
Y1 - 1991/1/1
N2 - 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.
AB - 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.
KW - 5′ flanking region
KW - DNase I hypersensitivity site
KW - mRNA transcript stability
KW - Polymorphism
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=0026042309&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026042309&partnerID=8YFLogxK
U2 - 10.1172/JCI115255
DO - 10.1172/JCI115255
M3 - Article
C2 - 1674946
AN - SCOPUS:0026042309
VL - 87
SP - 2207
EP - 2215
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 6
ER -