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Type-I interferons are potent inhibitors of interleukin-8 production in
hematopoietic and bone marrow stromal cells
MJ Aman, G Rudolf, J Goldschmitt, WE Aulitzky, C Lam, C Huber and C Peschel
Department of Medicine, Johannes-Gutenberg University, Mainz, Germany.
Interleukin-8 (IL-8) is produced by many cell types upon stimulation with
bacterial products or inflammation-associated cytokines such as tumor
necrosis factor-alpha and IL-1. Interferons (IFNs) represent another group
of cytokines that are induced by similar stimuli in inflammatory reactions.
We show now that type-I IFNs are potent inhibitors of IL-8 expression in
vitro and in vivo. A significant reduction of both secretion of IL-8
protein and accumulation of IL-8 mRNA in vitro was observed in several cell
types comprising peripheral blood mononuclear cells (PBMNC) from healthy
donors and from patients with chronic myelogenous leukemia (CML), the
myelomonocytic cell line THP-1, and bone marrow (BM) stromal cells as a
representative model for BM microenvironment. By contrast, in
lipopolysaccharide-stimulated polymorphonuclear phagocytes IFN failed to
suppress IL-8 expression. In untreated patients with CML, a constitutive
expression of IL-8 mRNA was detected in freshly isolated PBMNC that was
markedly reduced 5 hours after therapeutic application of IFN-alpha. The
mechanism of IL-8 downregulation was studied more in detail in the THP-1
cell line. The experiments showed that de novo protein synthesis was not
required for the inhibitory effect. RNA decay analysis and nuclear run-on
assays suggest that in THP-1 cell line the inhibition of IL-8 expression is
predominantly regulated at the posttranscriptional level.
Volume 82,
Issue 8,
pp. 2371-2378,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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