Interleukin-8 gene expression in human bronchial epithelial cells. Academic Article uri icon

Overview

MeSH

  • Cells, Cultured
  • Chemotaxis, Leukocyte
  • Epithelial Cells
  • Epithelium
  • Gene Expression
  • Humans
  • Luciferases
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha
  • Up-Regulation

MeSH Major

  • Bronchi
  • Interleukin-8

abstract

  • The capacity of cells of the human bronchial epithelium to express the gene for interleukin-8 (IL-8) was evaluated in bronchial epithelium derived cell lines, HS-24 and BET-1A, using tumor necrosis factor-alpha (TNF) as a model inflammatory stimulus. As in other epithelium, TNF markedly increased the level of the 1.8-kilobase IL-8 mRNA transcripts in both bronchial epithelial cell lines. In HS-24 cells, nuclear run-on analyses showed the IL-8 gene transcription rate was dramatically increased, more than 30-fold, after TNF stimulation. The half-life of IL-8 mRNA transcripts in these cells was approximately 40 min and did not change after TNF stimulation, suggesting that TNF up-regulated IL-8 gene expression mainly at the transcriptional level. DNase I hypersensitivity site mapping of chromatin DNA in resting HS-24 cells demonstrated two hypersensitivity sites within 400 base pairs (bp) 5' to exon I and one site within exon I. However, after TNF stimulation, the exon I hypersensitivity site disappeared and a new site approximately 120 bp 5' to exon I emerged. Consistent with these observations, transfection studies with HS-24 cells using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene demonstrated potent promoter activity in a 174-bp segment (-130 to +44 relative to the transcription start site), which also exhibited a response to TNF, while a segment from -112 to +44 showed very low promoter activity and no response to TNF. Thus, human bronchial epithelial cells can express the IL-8 gene, with expression in response to the inflammatory mediator TNF regulated mainly at the transcriptional level, and with elements within the 5'-flanking region of the gene that are directly or indirectly modulated by the TNF signal.

publication date

  • October 15, 1991

has subject area

  • Bronchi
  • Cells, Cultured
  • Chemotaxis, Leukocyte
  • Epithelial Cells
  • Epithelium
  • Gene Expression
  • Humans
  • Interleukin-8
  • Luciferases
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 1918068

Additional Document Info

start page

  • 19611

end page

  • 19617

volume

  • 266

number

  • 29