INTERLEUKIN-8 PRODUCTION BY THE HUMAN COLON EPITHELIAL-CELL LINE HT-29 - MODULATION BY INTERLEUKIN-13

Citation
G. Kolios et al., INTERLEUKIN-8 PRODUCTION BY THE HUMAN COLON EPITHELIAL-CELL LINE HT-29 - MODULATION BY INTERLEUKIN-13, British Journal of Pharmacology, 119(2), 1996, pp. 351-359
Citations number
49
Categorie Soggetti
Pharmacology & Pharmacy",Biology
ISSN journal
00071188
Volume
119
Issue
2
Year of publication
1996
Pages
351 - 359
Database
ISI
SICI code
0007-1188(1996)119:2<351:IPBTHC>2.0.ZU;2-Y
Abstract
1 We have determined which cytokines induce and modulate the productio n of the chemokine interleukin-8 (IL-8) by the human colonic epithelia l cell line HT-29. 2 Growth arrested cell cultures were stimulated wit h the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tu mour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-13 (IL-13), interleukin-10 (IL-10) or vehicle added alone or in combination. The production of IL-8 was determined by enzyme-lin ked immunosorbent assay (ELISA) and IL-8 messenger RNA expression by N orthern blot analysis. 3 The production of IL-8 in unstimulated cells was undetectable by both ELISA and Northern blot analysis. 4 HT-29 cel ls produced IL-8 following stimulation with IL-1 alpha or TNF-alpha in a time- and a concentration-dependent manner, while IFN-gamma, IL-10 and IL-13 did not induce IL-8 production by HT-29 cells. 5 IL-13 was f ound to up-regulate significantly (P<0.01) the IL-1 alpha but not the TNF-alpha-induced IL-8 generation by HT-29 cells. In contrast, IL-10 h ad no effect on either IL-1 alpha or TNF-alpha-induced IL-8 production . 6 Experiments using cycloheximide demonstrated that this synergistic effect of IL-13 and IL-1 alpha on IL-8 secretion was not through de n ovo protein synthesis. Using actinomycin-D, we demonstrated that the I L-13 up-regulation was at the level of transcription rather than messe nger RNA stability. 7 These findings suggest that colonic epithelial c ells have a functional IL-13 receptor, which is coupled to an up-regul ation of IL-1 alpha, but not TNF-alpha induced IL-8 generation.