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) was analyzed in rat brain endothelium cultures after cytokine stimulation. SP secretion was found after stimulation with high doses of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). High doses of interferon-gamma (INF-gamma) had no effect on this secretion. Elevated SP release was found to be associated with mRNA expression of beta-preprotachykinin (beta-PPT), precursor of SP, in the cells. Under cytokine stimulation, part of SP was bound to brain endothelial cell surface, suggesting the existence of an autocrine network for this neuropeptide. These findings suggest that SP may have an immunomodulatory action at the blood-brain barrier during inflammatory and autoimmune processes in the central nervous system.
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PMID:Enhanced secretion of substance P by cytokine-stimulated rat brain endothelium cultures. 960 Jul 11

Neuropeptides mediate stress-induced cutaneous inflammation such as atopic dermatitis. The effect of substance P on proliferation and cytokine mRNA expression of peripheral blood mononuclear cells in response to Dermatophagoides farinae (Der f) was studied in atopic dermatitis patients with positive RAST scores to Der f. Upon stimulation with Der f peripheral blood mononuclear cells from patients proliferated in a B7-dependent (CD80- and CD86-dependent) manner, while those from the patients with negative scores, nonatopic eczematous dermatitis patients or normal individuals, did not. Based on the reactivity of normal individuals, atopic dermatitis patients with a stimulation index greater than 1.8 were tentatively defined as high responders, who comprised two-thirds of the patients. Proliferation in high responders was associated with upregulation of IL-2 mRNA expression and induction of IL-5 mRNA expression. Substance p at 10(-10) to 10(-8) M promoted the Der f-induced proliferation when added at the start of culture and upregulated IL-10 MRNA expression while downregulating IL-5 mRNA expression. Our results suggest that substance P modifies immune responses of atopic T cells to Der f by promoting proliferation and altering cytokine profiles, and thus modulates the clinical manifestations of atopic dermatitis.
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PMID:Regulation of peripheral blood mononuclear cell responses to Dermatophagoides farinae by substance P in patients with atopic dermatitis. 961 38

Murine schistosomiasis mansoni is a parasitic disease in which flukes living in the portal vein of the host produce ova that deposit in the liver and intestines. In these organs, ova release antigens that induce chronic, focal granulomatous inflammation. IFN-gamma is an inflammatory cytokine important in macrophage activation and B-cell differentiation. A substance P (SP)/somatostatin (SOM) neurokine immunoregulatory circuit controls IFN-gamma production in schistosome granulomas. SP stimulates, while SOM inhibits IFN-gamma release, modulating IFN-gamma-dependent circuitry. SP and SOM function through interaction with authentic SP and SOM receptors located on granuloma T cells. Also, the granulomas produce authentic SP and SOM14, as evidenced by the presence of mRNA and product. The granulomas have no nerves. This, and other data suggest that the inflammatory cells make these neurokines. Granuloma macrophages produce SOM. Macrophages from various sources express SOM mRNA in response to LPS, IFN-gamma, IL-10 or several other inflammatory mediators. Thus, the inflammation of murine schistosomiasis has a complete SP/SOM immunoregulatory circuit, which in turn is subject to immunoregulation.
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PMID:The substance P and somatostatin interferon-gamma immunoregulatory circuit. 962 80

Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immune deficiency syndrome together with an encephalopathy characterized by impairments in spatial learning and memory. These cognitive deficits are evident before the appearance of neuron loss and lymphoid cell invasion of the brain. Nonetheless, a prominent gliosis and a variety of neurochemical changes precede the development of cognitive deficits. The neurochemical abnormalities include significant decreases in striatal Met-enkephalin and substance P (but not somatostatin), increases in concentrations of quinolinic acid and platelet-activating factor, and alterations in brain fyn kinase. At this stage of the infection, some of these neurochemical changes can be reversed by glutamate receptor antagonists, cytokine inhibitors, and anti-retroviral agents. In later stages of the infection, however, the infected mice develop irreversible neuronal loss, invasion of hematopoietic cells, and increased viral burden in the CNS. In addition, motor-neuron dysfunction (hindlimb paralysis, weakness, and ataxia) and seizures are sometimes observed during the late stages of infection. Thus, the LP-BM5 MuLV-infected mouse is a useful model for studying the chronology of neurodegenerative changes, ranging from reversible neuron dysfunction to irreversible neuron loss, that are associated with retrovirus-induced immunodeficiency.
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PMID:The encephalopathy associated with murine acquired immunodeficiency syndrome. 962 8

The cutaneous nervous system recently has been demonstrated to interact with multiple target cells in the skin and to mediate actions important in inflammatory conditions. Neuropeptides released by cutaneous neurons such as substance P (SP), vasointenstinal peptide (VIP), calcitonine gene regulated peptide (CGRP), proopiomelancortin (POMC) peptides and others modulate the function of immunocompetent and inflammatory cells as well as epithelial and endothelial cells. They have been found to function as mediators of cell proliferation, cytokine and growth factor production as well as adhesion molecule and cell surface receptor expression. In addition many cells including keratinocytes, fibroblasts, endothelial cells and inflammatory cells have been shown to release several neuropeptides and they express their corresponding receptors. These findings indicate that neuropeptides participate in the complex network of mediators that regulate cutaneous inflammation, hyperproliferation and wound healing.
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PMID:Neuropeptides: role in inflammatory skin diseases. 964 21

Though immune outcome is known to be determined by which helper T cell response predominates, no local mechanism has yet been established which can explain how the neuronal system may control this. It is possible that the nervous system releases neuropeptides at specific local sites of infection or challenge, which triggers lymphocytes at those points to release specific cytokine profiles. These may then influence the direction of the Th1/Th2 response and therefore immune outcome. The aim of this study was to evaluate whether and if so how neuropeptides influence cytokine production by lymphocytes, especially T cells. We investigated the effects of neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal peptide (VIP) on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by stimulating nonadherent splenocytes and helper T cell clones with antigens in vitro in the presence or absence of these peptides. NPY greatly enhanced IL-4 production and inhibited IFN-gamma. CGRP inhibited IFN-gamma production markedly in a dose-dependent manner, but had no effects on IL-4 production. SP and VIP had no effects on IFN-gamma production, but SP enhanced and VIP suppressed IL-4 production slightly but consistently. Therefore neuropeptides can influence cytokine production. This opens the door to speculations that these specific cytokine profiles might play a part in influencing the direction of the consequent Th1/Th2 cascade and immune outcome and possibly the pathogenesis of immune-related diseases.
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PMID:Differential effects of neuropeptides on cytokine production by mouse helper T cell subsets. 969 53

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane of multiple joints. This inflammatory microenvironment allows fibroblast-like synoviocytes (FLS) to express or enhance several adhesion or costimulatory molecules. This phenotypic shift, under proinflammatory cytokines, seems to be related to functional consequences for antigen presentation to T cells. The sensory neuropeptide substance P (SP), present at high levels, is able to act on FLS proliferation and enzyme secretion. These data led us to investigate whether SP could also provoke a phenotypic change of FLS. Using flow cytometry and a three-step cellular ELISA method, we determined whether SP has an influence on the expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1), VCAM-1, LFA-3, CD40, B7.1 or B7.2 molecules on RA FLS incubated with interferon-gamma (IFN-gamma) or IL-1beta or tumour necrosis factor-alpha (TNF-alpha) with or without SP. Our results indicate that SP potentiates the effect of proinflammatory cytokines on the expression of VCAM-1 on RA FLS. We verified the presence of specific SP (NK1) receptor mRNA. Using reverse transcription-polymerase chain reaction, we showed that RA FLS of patients express NK1 receptor mRNA. These results suggest that SP increase of cytokine-induced VCAM-1 expression acts via this specific SP receptor. Thus, during chronic inflammation RA FLS are at the interface between the immune and the nervous systems.
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PMID:Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes. 971 78

Tachykinin NK1 receptors play an important role in the development of neurogenic inflammatory responses. We have used the murine air-pouch model to investigate whether the neurogenic component of the cellular inflammatory response to interleukin-1beta (IL-1beta, 10 ng into the air-pouch) is altered in NK1 receptor knockout mice compared to wild type controls. Air-pouches were washed following a 4 h IL-1beta treatment, the wash collected and neutrophil number estimated using a Neubauer haemocytometer. The response to IL-1beta was significantly attenuated in NK1 receptor +/- (40% reduction) and -/- mice (62% reduction) compared to wild type controls (+/+), whilst the response to cytokine-induced neutrophil chemoattractant (CINC, 0.3 microg) was unaffected. The response to substance P (7.5 nmol) was attenuated by approximately 50% in both NK1 receptor +/- and -/- mice compared to wild type controls. In conclusion NK1 receptors play a significant role in the cellular response to IL-1beta in a model of inflammation.
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PMID:Impaired IL-1beta-induced neutrophil accumulation in tachykinin NK1 receptor knockout mice. 972 Jul 67

Searching for nervous system candidates that could directly induce T cell cytokine secretion, I tested four neuropeptides (NPs): somatostatin, calcitonin gene-related peptide, neuropeptide Y, and substance P. Comparing neuropeptide-driven versus classical antigen-driven cytokine secretion from T helper cells Th0, Th1, and Th2 autoimmune-related T cell populations, I show that the tested NPs, in the absence of any additional factors, directly induce a marked secretion of cytokines [interleukin 2 (IL-2), interferon-gamma, IL-4, and IL-10) from T cells. Furthermore, NPs drive distinct Th1 and Th2 populations to a "forbidden" cytokine secretion: secretion of Th2 cytokines from a Th1 T cell line and vice versa. Such a phenomenon cannot be induced by classical antigenic stimulation. My study suggests that the nervous system, through NPs interacting with their specific T cell-expressed receptors, can lead to the secretion of both typical and atypical cytokines, to the breakdown of the commitment to a distinct Th phenotype, and a potentially altered function and destiny of T cells in vivo.
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PMID:Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. 977 May 22

The inhibitory effect of inflammation and endotoxins on the secretion of reproductive hormones from the hypothalamo-pituitary axis is well documented. A comparison of the luteinizing hormone (LH) suppressing effects of several pro-inflammatory cytokines revealed that centrally administered IL-1 beta was the most potent inhibitor of pituitary LH secretion; interleukin (IL)-1 alpha and tumor necrosis factor (TNF) alpha were relatively less effective, whereas IL-6 was ineffective. This order of potency suggested that the anti-gonadotropic effects of an immune challenge are most likely attributable to the action of centrally released IL-1 beta, and this was supported by the demonstration that IL-1 beta suppressed hypothalamic luteinizing hormone releasing hormone (LHRH) release. We used a multifaceted approach to identify the afferent signals in the brain that convey immune messages to hypothalamic LHRH neurons. Pharmacological studies with specific antagonists of opioid receptor subtypes demonstrated that activation of the mu 1 receptor subtype was required to transmit the cytokine signal. Furthermore, icv IL-1 beta upregulated hypothalamic POMC mRNA and increased the concentration and release of beta-endorphin, the primary ligand of mu 1 receptors. We have obtained evidence that IL-1 beta also enhanced the gene expression and concentration of tachykinins, a family of nociceptive neuropeptides in the hypothalamus. Blockade of tachykinergic NK2 receptors attenuated IL-1 beta induced inhibition of LH secretion. Collectively, these results demonstrate that IL-1 beta, generated centrally in response to inflammation, upregulates the opioid and tachykinin peptides in the hypothalamus. These two groups of neuropeptides are critically involved in relaying the cytokine signal to neuroendocrine neurons and causing the suppression of hypothalamic LHRH and pituitary LH release.
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PMID:The anti-gonadotropic effects of cytokines: the role of neuropeptides. 978 36


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