We recently showed that lipopolysaccharide (LPS) is a potent inducer of interleukin-8 (IL-8) expression in human polymorphonuclear leucocytes (PMN), at the level of both mRNA and protein, and that interferon-gamma (IFN gamma) inhibits IL-8 mRNA accumulation in stimulated PMN. To further define the molecular basis of the regulation of IL-8 gene expression in PMN, we investigated the effects of LPS and IFN gamma at both the transcriptional and post-transcriptional levels. As determined by Northern blot analysis, new protein synthesis was not required for the induction of IL-8 mRNA expression by LPS. Neither did the half-life of IL-8 mRNA in LPS-treated PMN differ from that observed in untreated cells. However, nuclear run-on analysis revealed that LPS increased the transcription of the IL-8 and IL-1 beta genes and that, in LPS-activated cells, IFN gamma markedly inhibited the rate of IL-8 gene transcription, but not that of IL-1 beta. IFN gamma did not affect IL-8 mRNA stability in LPS-treated PMN, indicating that the cytokine does not regulate LPS-induced IL-8 gene expression through post-transcriptional events. These results provide the first evidence that human granulocytes can actively transcribe the IL-8 gene, and that transcriptional inhibition is the mechanism by which IFN gamma inhibits IL-8 gene expression in PMN.
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September 1995
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Research Article|
September 15 1995
Lipopolysaccharide-induced interleukin-8 gene expression in human granulocytes: transcriptional inhibition by interferon-γ Available to Purchase
M A Cassatella;
M A Cassatella
*Department of General Pathology, University of Verona, 37134 Verona, Italy
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S Gasperini;
S Gasperini
*Department of General Pathology, University of Verona, 37134 Verona, Italy
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F Calzetti;
F Calzetti
*Department of General Pathology, University of Verona, 37134 Verona, Italy
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P P McDonald;
P P McDonald
*Department of General Pathology, University of Verona, 37134 Verona, Italy
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G Trinchieri
G Trinchieri
†Wistar Institute, Philadelphia, PA 19104, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1995 The Biochemical Society, London
1995
Biochem J (1995) 310 (3): 751–755.
Citation
M A Cassatella, S Gasperini, F Calzetti, P P McDonald, G Trinchieri; Lipopolysaccharide-induced interleukin-8 gene expression in human granulocytes: transcriptional inhibition by interferon-γ. Biochem J 15 September 1995; 310 (3): 751–755. doi: https://doi.org/10.1042/bj3100751
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