Interleukin‐8 production by the human colon epithelial cell line HT‐29: modulation by interleukin‐13

• Published in: British journal of pharmacology Vol. 119; no. 2; pp. 351 - 359
• Main Authors: Kolios, George, Robertson, Duncan A.F., Jordan, Nicola J., Minty, Adrian, Caput, Daniel, Ferrara, Pascal, Westwick, John
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.1996; Nature Publishing
• Subjects: Biological and medical sciences; Chemokines; colon epithelial cells; Drug Synergism; Gastroenterology. Liver. Pancreas. Abdomen; HT29 Cells - drug effects; HT29 Cells - metabolism; HT‐29; Humans; inflammatory bowel disease; Interleukin-1 - pharmacology; Interleukin-10 - pharmacology; Interleukin-13 - pharmacology; Interleukin-8 - biosynthesis; Interleukin-8 - metabolism; interleukin‐13; interleukin‐8; Medical sciences; Other diseases. Semiology; RNA, Messenger - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Human; Cell culture; Digestive system; Modulation; Interleukin 13; Colon; Epithelium; In vitro; Interleukin 8; Inflammatory disease
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15993.x

1 We have determined which cytokines induce and modulate the production of the chemokine interleukin‐8 (IL‐8) by the human colonic epithelial cell line HT‐29. 2 Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin‐1α (IL‐1α), tumour necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), interleukin‐13 (IL‐13), interleukin‐10 (IL‐10) or vehicle added alone or in combination. The production of IL‐8 was determined by enzyme‐linked immunosorbent assay (ELISA) and IL‐8 messenger RNA expression by Northern blot analysis. 3 The production of IL‐8 in unstimulated cells was undetectable by both ELISA and Northern blot analysis. 4 HT‐29 cells produced IL‐8 following stimulation with IL‐1α or TNF‐α in a time‐ and a concentration‐dependent manner, while IFN‐γ, IL‐10 and IL‐13 did not induce IL‐8 production by HT‐29 cells. 5 IL‐13 was found to up‐regulate significantly (P < 0.01) the IL‐1α but not the TNF‐α‐induced IL‐8 generation by HT‐29 cells. In contrast, IL‐10 had no effect on either IL‐1α or TNF‐α‐induced IL‐8 production. 6 Experiments using cycloheximide demonstrated that this synergistic effect of IL‐13 and IL‐1α on IL‐8 secretion was not through de novo protein synthesis. Using actinomycin‐D, we demonstrated that the IL‐13 up‐regulation was at the level of transcription rather than messenger RNA stability. 7 These findings suggest that colonic epithelial cells have a functional IL‐13 receptor, which is coupled to an up‐regulation of IL‐1α, but not TNF‐α induced IL‐8 generation.