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Substance P (SP) mediates production of stem cell factor and interleukin-1
in bone marrow stroma: potential autoregulatory role for these cytokines in
SP receptor expression and induction
P Rameshwar and P Gascon
UMDNJ-New Jersey Medical School, Department of Medicine, Newark 07103, USA.
Substance P (SP) is a neuropeptide widely distributed in the nervous
system. Its release within the bone marrow (BM) can mediate bidirectional
neurohematopoietic communication via specific receptors: neurokinin-1R
(NK-1R), NK-2R, or NK-3R. We have previously reported that SP effects on
hematopoiesis are mediated by an NK-1-type receptor, the BM stroma, and
growth factors. Here, we have studied the induction of stem cell factor
(SCF) and interleukin-1 (IL-1) by SP in stroma. At 10(-9) mol/L SP,
cytokine levels in supernatants were IL-1 alpha, 20 +/- 5 ng/mL; IL-1 beta,
40 +/- 10 ng/mL; and SCF, nondetectable; and the cell-associated levels
were SCF, 21 +/- 2 ng/mL; IL-1 alpha, 90 +/- 6 ng/mL; and IL-1 beta, 45 +/-
3 ng/mL. Reverse transcriptase-polymerase chain reaction and ligand-binding
studies with stroma stimulated by these two cytokines resulted in (1)
NK-1-like receptor mRNA accumulation and (2) downregulation of SP binding
sites (day 1) followed by an upregulation (day 3). Low numbers of
high-affinity receptors were expressed by day 1 but not by day 3. The
results indicate that SP induces IL-1 and SCF in stroma and that these
cytokines have the potential to autoregulate NK-R.
Volume 86,
Issue 2,
pp. 482-490,
07/15/1995
Copyright © 1995 by The American Society of Hematology
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