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The pro-inflammatory cytokine interleukin-8 (IL-8) is produced by HT29 colon epithelial cells following engagement of either CD95 or tumour necrosis factor (TNF) receptors. While the IL-8 promotor elements activated by TNF are well characterised, those responsible for induction of IL-8 by CD95 are unknown. We examined the pathway for CD95 induced IL-8 secretion using two luciferase reporter constructs; the first comprising approximately 500 bp of the IL-8 promotor that includes the nuclear factor kappa B (NFkappaB), C/EBP and AP-1 sites known to be involved in TNF mediated IL-8 induction; the second that encompasses these elements but extends approximately 1.1 kb further upstream. Although IL-8 mRNA and protein were produced in response to either TNF or CD95 ligation, only TNF induced an increase in the reporter activity of the promoter constructs. Nevertheless, IL-8 induction by CD95 resulted primarily from increased transcription and not from an increase in IL-8 mRNA stability. These results suggest that promoter elements/enhancers involved in CD95 mediated IL-8 induction are distinct from those used by TNF and not contained within the 1.6 kb region immediately upstream of the initiation codon.

Original publication

DOI

10.1006/cyto.2001.0915

Type

Journal article

Journal

Cytokine

Publication Date

21/07/2001

Volume

15

Pages

108 - 112

Keywords

Colon, Colonic Neoplasms, HT29 Cells, Humans, Interferon-gamma, Interleukin-8, Intestinal Mucosa, RNA, Messenger, Receptors, Tumor Necrosis Factor, Signal Transduction, Transcriptional Activation, Tumor Necrosis Factor-alpha, fas Receptor