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)

The granulomas of mice infected with Schistosoma mansoni for 8 wk have macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has no known function. To uncover the possible significance of SOM produced within this granulomatous inflammation, we sought SOM receptors on distinct cellular components of the granuloma to identify cells targeted for SOM action. [125I]SOM 1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly. Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide, a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1-28, substance P, and vasoactive intestinal peptide did not. The SOM receptor localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5 and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6) did not affect IL-5 production. Octreotide administered to animals in vivo decreased the intensity of the granulomatous response. Thus, some granuloma T cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may participate in regulation of the granulomatous response by modulating the secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics the action of SOM on the immune system.
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PMID:Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. 135 73

To investigate the role of IL-5 in airway hyperreactivity and pulmonary eosinophilia, we used a model of allergic asthma in guinea pigs and a neutralizing monoclonal antibody (TRFK-5) directed against murine IL-5. Sensitized guinea pigs were challenged with 1% ovalbumin (OVA) aerosol and assessed for airway eosinophilia (by bronchoalveolar lavage [BAL] and histologic evaluation of airway tissue) and bronchoconstrictor responsiveness to substance P (SP) (as RL100 and Cdyn40) 24 h later. OVA challenge of sensitized animals caused a significant increase in airway responsiveness to SP, with a 4.9-fold decrease in RL100 and a 4.7-fold decrease in Cdyn40. Accompanying this increased sensitivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4- to 5-fold increase in eosinophils in intrapulmonary bronchial tissue. Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA challenge blocked BAL and lung tissue increases in eosinophils but had no effect on the development of airway sensitivity to SP. In contrast, similar treatment with 30 mg/kg of this antibody blocked OVA-induced increased sensitivity to SP as well as BAL and lung tissue eosinophilia. These data suggest a critical and possibly independent role for IL-5 in allergic airway hyperresponsiveness and the accumulation of eosinophils within the lung of the guinea pig.
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PMID:Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma. 750 92

The effects of vasoactive intestinal peptide (VIP) on human IgA1 and IgA2 production were studied. In unfractionated small resting B cells stimulated with anti-CD40 monoclonal antibody (mAb), VIP induced IgA1 and IgA2 production without affecting the production of IgG1, IgG2, IgG3, IgG4, IgM, or IgE. When small B cells were separated into sIgA1+, sIgA2+, sIgA1- and sIgA2- B cells, anti-CD40 mAb plus VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2- B cells, respectively, while having no effect on sIgA1+ and sIgA2+ B cells. This induction by VIP was specific, since anti-CD40 mAb plus other neuropeptides, i.e., somatostatin or substance P, had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Further, anti-CD40 mAb plus various cytokines, including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor-beta, low molecular weight B cell growth factor, and interferon-gamma, did not induce IgA1 and IgA2 production by sIgA1- and sIgA2- B cells, respectively. These results indicate that in the presence of anti-CD40 mAb, VIP induces IgA1 and IgA2 production by isotype switching.
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PMID:Vasoactive intestinal peptide specifically induces human IgA1 and IgA2 production. 752 70

We studied the effects of vasoactive intestinal peptide (VIP) on IgA1 and IgA2 production in human fetal B cells and pre-B cells derived from bone marrow. VIP induced IgA1, IgA2, and IgM production in sIgM+, CD19+ fetal B cells stimulated with anti-CD40 monoclonal antibody (MoAb) without inducing the production of IgG1, IgG2, IgG3, IgG4, or IgE. The anti-CD40 MoAb plus VIP also induced IgA1, IgA2, and IgM production in sIgM-, CD19+ pre-B cells, which was enhanced by the addition of interleukin-7 (IL-7). This induction by VIP was specific, as the anti-CD40 MoAb plus other neuropeptides [ie, somatostatin (SOM) or substance P (SP)] had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Furthermore, the anti-CD40 MoAb plus various cytokines, including IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor beta (TGF-beta), low-molecular-weight B-cell growth factor (BCGF), and interferon-gamma (IFN-gamma), did not induce IgA1 and IgA2 production in fetal B cells or pre-B cells. These findings indicate that, in the presence of costimulators, VIP may induce IgA1 and IgA2 production by isotype switching.
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PMID:Induction of IgA1 and IgA2 production in immature human fetal B cells and pre-B cells by vasoactive intestinal peptide. 753 91

Human nasal mucosal samples exposed in vitro to substance P or allergenic Ag were tested for the mRNA of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, and IFN-gamma using specific reverse transcriptase-polymerase chain reaction assays. After the administration of substance P, at dosages ranging from 10(-6) to 10(-9) M, an enhanced expression of the mRNA for IL-1 beta, -3, -5, -6, TNF-alpha, and IFN-gamma was observed in all mucosal samples of allergic subjects and in half of the nonallergic subjects. The expression of IL-2 and IL-4 was low. Mucosal samples of allergic subjects showed an increased expression of mRNA for cytokines after administration of specific Ag, whereas no enhancement was observed in samples from nonallergic subjects. Our data suggest that substance P may regulate allergic reactions via enhanced production of certain regulatory cytokines.
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PMID:Cytokine expression after the topical administration of substance P to human nasal mucosa. The role of substance P in nasal allergy. 769 47

From current information, a brief review was made on the basic properties of a possible process of eosinophil activation and degranulation. The "activated" eosinophils show the following characteristics: diminished cell density, morphologic alterations, increased surface receptors, heightened parasite killing, increased metabolic activity and prolonged survival. Immune complexes (secretory IgA, IgG, IgE) are known as potent triggering stimuli of eosinophil degranulation as well as complement fragments (C3b, C3bi). Cytokines (IL-5, GM-CSF), PAF and peptides (substance P) act both as weak degranulation inducer and degranulation enhancer. Synergism between the two pathways, Ca2+ and protein kinase C, is now recognized as a common feature of control of secretion in eosinophils.
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PMID:[Eosinophil granule proteins (MBP, ECP, EPX/EDN, EPO)--a possible process of eosinophil activation and degranulation]. 849 33

Administration of interleukin 5 (IL-5) to guinea pigs by tracheal injection was associated with increased recovery of eosinophils and neutrophils from bronchoalveolar lavage (BAL) fluid. The number of eosinophils recovered from BAL fluid increased in a dose-dependent manner from 9 +/- 2 X 10(3)/ml to a plateau of 143 +/- 29 X 10(3)/ml after the administration of recombinant human IL-5 (rhIL-5). Tracheal administration of recombinant guinea pig IL-5 (gpIL-5) also increased eosinophil recovery but was less potent than rhIL-5. Histological analysis confirmed the presence of inflammatory cells in the lung; there were higher grades of inflammation in airway than in parenchymal tissue after gpIL-5 administration. In addition, the histological grade of airway inflammation was greater 24 and 72 h after gpIL-5 administration than it was 6 days after administration. Airway hyperresponsiveness is reported to occur in guinea pigs exposed to rhIL-5 by intraperitoneal cellular production. It is surprising that airway infiltration with eosinophils induced by the topical application of IL-5 was not associated with hyperresponsiveness to substance P, histamine, or platelet-activating factor in intact animals or to methacholine in tracheally perfused lungs. Furthermore, the microvascular leakage induced by substance P was not altered by rhIL-5 administration. These findings indicate that the presence of eosinophils alone is not sufficient for the expression of airway hyperresponsiveness. Our ability to separate eosinophil recruitment and retention in the tissues from airway hyperresponsiveness indicates that these two processes are distinct and that the presence of eosinophils in lung tissue, by itself, is not sufficient to alter airway contractile responses.
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PMID:Effects of interleukin 5-induced pulmonary eosinophilia on airway reactivity in the guinea pig. 863 29

In this study, we examined the mechanism by which bronchoalveolar lavage (BAL) cells induced hyperreactivity of the trachea in vitro. As both interleukin-5 (IL-5) and substance P (SP) appeared to be involved, the effect of these mediators was examined in vivo. Tracheae were incubated with BAL cells from ovalbumin or saline challenged animals, and from naive animals, in the absence or presence of either IL-5, SP, or both. In addition, the effect of intra-airway application of IL-5, SP, both, or vehicle on tracheal hyperreactivity was examined. Incubation of tracheae with BAL cells from ovalbumin challenged animals induced an increase (30 +/- 10%) in the maximal response to histamine. The hyperreactivity could be completely inhibited by co-incubation with 5-lipoxygenase inhibitor, AA861. The hyperreactivity could be mimicked by incubation of tracheae with BAL cells from naive animals in the presence of IL-5 and SP. After in vivo administration of either IL-5 or SP, maximal responses to histamine were increased and amounted to 105 +/- 35 and 101 +/- 37%, respectively. Administration of IL-5 but not SP induced a significant increase in the number of eosinophils (67 +/- 22%) and eosinophil peroxidase (EPO) activity (94 +/- 33%) in BAL cells. The simultaneous administration of IL-5 and SP did not potentiate the hyperreactivity and eosinophilia observed with IL-5 alone. These data suggest that IL-5 is important in the recruitment of eosinophils, whereas both IL-5 and substance P are involved in the induction of airway hyperreactivity.
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PMID:Role of interleukin-5 and substance P in development of airway hyperreactivity to histamine in guinea-pigs. 873 9

The effects of vasoactive intestinal peptide (VIP) on human immunoglobulin (Ig) production were studied in (1) B cell lines; (2) anti-CD40 mAb-stimulated B cells from non-atopic donors; and (3) unstimulated mononuclear cells from atopic patients. In B cell lines, GM-1056, IM-9, and CBL, VIP enhanced IgA1, IgG1 and IgM production, respectively, in a dose-dependent fashion, while the other neuropeptides somatostatin (SOM) or substance P (SP) failed to do so. Among the various cytokines examined including IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, and G-CSF. IL-6 and IL-10 also enhanced Ig production. However, VIP-induced enhancement of Ig production was specific, and was not mediated via these cytokines, since enhancement was blocked by the VIP antagonist, while SOM and SP antagonists, anti-IL-6 mAb, or anti-IL-10 Ab failed to do so. In anti-CD40 mAb-stimulated B cells from nonatopic donors, VIP selectively induced IgA1 and IgA2 production without affecting IgG1, IgG2, IgG3, IgG4, IgM, or IgE production. This stimulatory effect was specifically blocked by the VIP antagonist, but not by SOM or SP antagonists, anti-IL-5 mAb, anti-IL-10 Ab, or anti-TGF-beta Ab. VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2-B cells, respectively, while this agent had no effect on sIgA1+ and sIgA2+B cells. In contrast, in unstimulated mononuclear cells from atopic patients, VIP selectively inhibited spontaneous IgE and IgG4 production without affecting IgG1, IgG2, IgG3, IgM, IgA1, or IgA2 production. This inhibitory effect was specifically blocked by the VIP antagonist, but not by anti-IFN-alpha Ab, anti-IFN-gamma mAb, anti-IL-12 Ab, or anti-TGF-beta Ab. VIP did not inhibit IgE or IgG4 production in B cells or in B cells cultured with either T cells or monocytes. However, VIP inhibited IgE and IgG4 production when B cells were cultured with both T cells and monocytes.
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PMID:Vasoactive intestinal peptide differentially modulates human immunoglobulin production. 879 Jul 85

The first week of dietary magnesium deficiency in rodent models is characterized by the induction of raised levels of neuropeptides (substance P [SP] and calcitonin gene related peptide [CGRP]), followed shortly thereafter by inflammatory cytokine release. Since neuropeptides participate in neurogenic inflammation, we have proposed that the neurogenic inflammatory response plays a role in the pathology of magnesium deficiency. However, the association between the early neuropeptide release and the subsequent pathology in this model remains unclear. Peripheral blood T lymphocytes were obtained from Balb/c mice fed a magnesium-deficient diet (approximately 1.8 mmol Mg/kg), or the same diet supplemented with 20 mmol MgO/kg. These cells were incubated in medium containing 10(-10) to 10(-5) M SP, after which the cells were examined for expression of SP receptors and the supernatants were collected and examined by immunochemical techniques for the presence of T lymphocyte associated cytokines. SP stimulation induced the secretion of interleukin (IL)-2, 4, 5, 10, 12, 13 and interferon-gamma (IFN-gamma). T lymphocytes from magnesium-deficient animals, when compared to magnesium-sufficient ones, secreted increased levels of these cytokines. The secretion of these cytokines was maximal at either 5 days (IL-4, IL-5) or 7 days (II-2, IL-10, and IFN-gamma) of magnesium deficiency. This increased sensitivity to SP appears to be related to an increased expression of SP receptors on the surface of T lymphocytes during the first week of magnesium deficiency. These data indicate that SP released early during magnesium deficiency exerts a regulatory role on T lymphocyte cytokine production, especially those cytokines regulating mast cell and immune responses leading to the onset of an immunopathological state.
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PMID:Immunoregulation by neuropeptides in magnesium deficiency: ex vivo effect of enhanced substance P production on circulating T lymphocytes from magnesium-deficient mice. 881 89


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