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Stimulation of interleukin-6 production by endothelin in rat bone
marrow-derived stromal cells
T Agui, X Xin, Y Cai, T Sakai and K Matsumoto
Institute for Experimental Animal Science, Nagoya City University Medical
School, Japan.
Endothelin (ET) produced by endothelial cells has recently been found to be
a potent vasoconstricting hormone. In this report, ET is shown to be a
potent stimulator of interleukin-6 (IL-6) production by rat bone marrow
(BM)-derived stromal cells. It was also shown that ET increased the level
of mRNA for IL-6 in these cells. The two types of ET receptor (R), ETAR and
ETBR, were shown to be expressed on both BM-derived stromal cells in
culture and ex vivo in BM tissue, suggesting that ET works as a physiologic
stimulator of IL-6 production in the BM. It was shown that ETAR is coupled
to phospholipase C activation, leading to the production of inositol
1,4,5-trisphosphate (IP3) and 1,2- diacylglycerol (DAG) as second
messengers in BM-derived stromal cells. This was corroborated by data
showing that IL-6 production in these cells was induced by combined
stimulation with ionomycin and phorbol myristate acetate, thereby bypassing
the effects of IP3 and DAG, respectively. This is the first report on the
hormonal regulation of IL- 6 production by BM stromal cells, indicating
that hematopoiesis is subject to endocrinologic regulation under
physiologic conditions. ET has recently been reported to be produced by
macrophages in response to bacterial lipopolysaccharide and human
immunodeficiency virus-1 glycoprotein 120. These facts, taken together with
our findings, raise the possibility that ET shares the same role of IL-1 as
a local cytokine, mediating an intercellular signal between macrophages and
BM stromal cells in response to bacterial or viral stimulation.
Volume 84,
Issue 8,
pp. 2531-2538,
10/15/1994
Copyright © 1994 by The American Society of Hematology
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