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Interferon-gamma upregulates interleukin-8 gene expression in human
monocytic cells by a posttranscriptional mechanism
MC Bosco, GL Gusella, I Espinoza-Delgado, DL Longo and L Varesio
Laboratory of Experimental Immunology, BRMP, National Cancer Institute-
Frederick Cancer Research and Development Center, MD 21702-1201.
Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine
that is produced in response to several stimuli. Because monocytic cells
are important producers of IL-8, we investigated whether interferon-gamma
(IFN-gamma), a potent inducer of activation and differentiation of
mononuclear phagocytes, affected IL-8 expression in this cell lineage. We
found a low constitutive level of IL-8 mRNA expression that was upregulated
by IFN-gamma in a dose- and time- dependent manner and via a
protein-synthesis-dependent process in the human monocytic cell line U937.
IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on
experiments showed that the IL- 8 gene was transcriptionally active in
control cells and that IFN-gamma did not enhance the transcriptional
activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the
stabilization of the mRNA and, therefore, controlled primarily at a
posttranscriptional level. These results represent the first evidence that
IFN-gamma upregulates IL-8 gene expression in cells of the monocytic
lineage, and show the involvement of posttranscriptional mechanisms in the
induction of IL-8 mRNA.
Volume 83,
Issue 2,
pp. 537-542,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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