title: 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.
abstract: 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.
authors.affiliation: UMDNJ-New Jersey Medical School, Department of Medicine, Newark 07103, USA.
authors.forename: P
authors.initials: P
authors.lastname: Rameshwar
authors.forename: P
authors.initials: P
authors.lastname: Gascón
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003238:Connective Tissue / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D008969:Molecular Sequence Data; D015213:Neuroimmunomodulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D019089:Stem Cell Factor; D013373:Substance P; C042867:spantide