Interleukin-8 gene expression in human bronchial epithelial cells*

H. Nakamura, K. Yoshimura, H. A. Jaffe, Ronald Crystal

Research output: Contribution to journalArticle

214 Citations (Scopus)

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-α (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.

Original languageEnglish
Pages (from-to)19611-19617
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number29
Publication statusPublished - 1 Jan 1991
Externally publishedYes

Fingerprint

Interleukin-8
Gene expression
Tumor Necrosis Factor-alpha
Epithelial Cells
Gene Expression
Genes
Exons
Base Pairing
Hypersensitivity
Epithelium
5' Flanking Region
Cells
Cell Line
Messenger RNA
Cell Fusion
Transcription Initiation Site
Deoxyribonuclease I
Transcription
Luciferases
Reporter Genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nakamura, H., Yoshimura, K., Jaffe, H. A., & Crystal, R. (1991). Interleukin-8 gene expression in human bronchial epithelial cells*. Journal of Biological Chemistry, 266(29), 19611-19617.

Interleukin-8 gene expression in human bronchial epithelial cells*. / Nakamura, H.; Yoshimura, K.; Jaffe, H. A.; Crystal, Ronald.

In: Journal of Biological Chemistry, Vol. 266, No. 29, 01.01.1991, p. 19611-19617.

Research output: Contribution to journalArticle

Nakamura, H, Yoshimura, K, Jaffe, HA & Crystal, R 1991, 'Interleukin-8 gene expression in human bronchial epithelial cells*', Journal of Biological Chemistry, vol. 266, no. 29, pp. 19611-19617.
Nakamura, H. ; Yoshimura, K. ; Jaffe, H. A. ; Crystal, Ronald. / Interleukin-8 gene expression in human bronchial epithelial cells*. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 29. pp. 19611-19617.
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