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

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-BR, 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 (SGF) 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. (C) 1995 by The American Society of Hematology.