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Chemokine gene expression in bone marrow stromal cells: downregulation with
sodium salicylate
SC Gautam, KR Pindolia, CJ Noth, N Janakiraman, YX Xu and RA Chapman
Division of Hematology/Oncology, Henry Ford Hospital, Detroit, MI 48202,
USA.
Chemotactic cytokines, chemokines, have been shown to influence the
proliferation of hematopoietic progenitor cells. Thus, regulation of
chemokine production by bone marrow accessory cells is a critical aspect of
stromal cell regulation of hematopoiesis. We have previously reported that
monocyte chemotactic protein-1 (MCP-1 or MCP-1/JE) and interferon inducible
protein 10 kD (IP-10) are both induced in murine bone marrow stromal cells
+/(+)-1.LDA11 after stimulation with the inflammatory agents interleukin-1
alpha (IL-1 alpha), interferon-gamma (IFN-gamma), or lipopolysaccharide
(LPS). In the present study, we have investigated the effect of sodium
salicylate, an antiinflammatory agent, on the IL-1 alpha-induced expression
of MCP-1/JE and IP-10 genes in stromal cells. Sodium salicylate attenuates
the levels of MCP-1/JE and IP-10 mRNA in a concentration- and
time-dependent manner. The suppression of MCP-1/JE mRNA is reversible,
whereas IP-10 mRNA expression is more or less irreversibly affected as its
recovery from the effect of sodium salicylate is slow and partial. Sodium
salicylate- mediated suppression of mRNA expression is attributable neither
to de novo synthesis of intermediary protein(s) nor to the destabilization
of mature mRNA transcripts. On the other hand, sodium salicylate
downregulates the transcriptional activity of both genes. Furthermore, IL-1
alpha induces activation of transcription factor nuclear factor (NF)-kB,
and sodium salicylate suppresses it in a dose-dependent manner. We conclude
that while posttranscriptional events remain unaffected, inhibition of
NF-kB activation by sodium salicylate may account for the suppression of
chemokine gene expression at the transcriptional level.
Volume 86,
Issue 7,
pp. 2541-2550,
10/01/1995
Copyright © 1995 by The American Society of Hematology
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