Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P (SP) is a neuropeptide which has been reported to have immunomodulatory activity. Most studies on SP have been performed on cells of the peripheral immune system. More recently, SP has been reported to have stimulatory activity on human bone marrow cells in vitro, and this activity was dependent on the presence of an adherent layer of cells. The in vitro adherent layer represents the stromal cells of the marrow. In this study, we directly addressed the effect of SP on cultured bone marrow stromal cells. Since stromal cells play an important role in the regulation of hematopoiesis, interactions of neuropeptides such as SP with this cell population could lead to an alteration of stem cell development within the bone marrow. Previously we have shown that SP stimulates protein synthesis in this cell population with two waves of protein synthesis activation, after 2 hr and 48 hr of SP incubation. In this study, we asked whether levels of known stromal cell cytokines were altered in response to SP incubation. We assayed the levels of Interleukin-7 (IL-7) and Stem Cell Factor (SCF) associated with the stromal cell surface following 2 hr and 48 hr of SP incubation. Cells were stimulated with SP for 2 hr or 48 hr. Following SP incubation, cells were washed and the levels of cell associated cytokine was determined by ELISA. Following 2 hr of treatment, 0.1 nM of SP significantly increased (p = 0.05) the level of IL-7 as compared to untreated controls. After 48 hr of treatment, 1, 10, and 100 nM SP significantly increased the levels of IL-7 in this cell population. When SCF levels were assayed, SP at all concentrations tested was found to increase significantly the levels of SCF following 2 hr of incubation. Following 48 hr of incubation, 10 and 100 nM of SP significantly increased the levels of SCF. The ability of SP to affect cytokine levels varied with time. Following 2 hr of SP incubation, cytokine levels were enhanced at the lower end of the concentration range as compared to 48 hr of SP treatment. A 48 hr incubation with SP yielded the highest levels of cytokine at the higher end of the concentration range. Taken together, the results of these studies suggest that SP has an immunoregulatory effect on bone marrow stromal cells leading to alteration in the production and/or secretion of regulatory cytokines such as IL-7 and SCF.
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PMID:Substance P mediated stimulation of cytokine levels in cultured murine bone marrow stromal cells. 864 13

JP05 (originally referred to as glucocorticoid-induced receptor gene or cDNA clone 4.2) designates a gene originally isolated from murine thymoma WEHI-7TG cells after being treated with glucocorticoids and forskolin. This gene is also induced by dexamethasone (a potent glucocorticoid receptor agonist) in isolated normal murine thymocytes. The predicted amino acid sequence was found to share significant similarity to the family of G-protein-coupled receptors, in particular to the tachykinin receptors NK-1, NK-2 and NK-3, with which it has an overall identity of 32%, 31% and 33%, respectively. The results of the present in situ hybridization analysis reveal that JP05 mRNA containing cells are extensively distributed throughout the rostrocaudal extension of the brain and spinal cord. However, the vast majority of the areas with high to moderate levels of JP05 mRNA were localized in the forebrain, primarily within limbic system structures, the dorsal and ventral striatum and in some hypothalamic nuclei. These results are discussed in relation to the central nervous system distribution of glucocorticoid receptor-containing cells and to the tachykinin system.
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PMID:Distribution of a glucocorticoid-induced orphan receptor (JP05) mRNA in the central nervous system of the mouse. 967 27

Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions-angiogenesis, fibroblast proliferation, and stimulation of BM progenitors-are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 +/-12 vs 18 +/-3; P <.01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research. (Blood. 2001;97:3025-3031)
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PMID:Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis. 1134 27