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

Cytokine hypersecretion might be involved in the onset and maintenance of depressive disorders and it has been suggested that St. John's wort extracts (Hypericum perforatum, SJW) might exert their antidepressant-like effects by affecting peripheral interleukin-6 (IL6) expression. We found that hyperforin, one putative active principle of SJW, and its dicyclohexylammonium salt (hyperforin-DCHA), inhibited the substance P (SP)-induced [L6 release inhuman astrocytoma cells (U373MG) with an Cs50 of 1.6 pM, indicating that hyperforin is likely to account for the inhibitory effect previously found in the same experimental model with SJW ex-tracts. [3H]SP binding experiments in parallel on the same intact cells indicate that hyperforin-DCHA does not interact with neuro-kinin-I receptors but very likely interacts with some intracellular steps leading to the synthesis and/or release of IL6. Hyperforin-DCHA also inhibited, with a similar IC50, the IL6 release induced in U373MG cells by two other classic proinflammatory stimuli,ILl and lipopolysaccharide (LPS), as well as the LPS-induced IL6 release in whole rat blood. Hyperforin-DCHA was less active in whole human blood. The concentrations required in vitro to inhibit LPS-induced IL6 release from rat and human whole blood are about one order of magnitude higher than the hyperforin levels measured in the plasma of rats or humans treated with pharmaco-logically active doses of SJW or hyperforin-DCHA.
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PMID:In vitro effects of the dicyclohexylammonium salt of hyperforin on interleukin-6 release in different experimental models. 1530 61

Cardiac ischemia-reperfusion alters sympathetic neurotransmission in the heart, but little is known about its effect on neuropeptide expression in sympathetic neurons. Ischemia followed by reperfusion induces the production of inflammatory cytokines in the heart, including interleukin-6 and cardiotrophin-1. These cytokines and related molecules inhibit the expression of neuropeptide Y (NPY), and stimulate the expression of vasoactive intestinal peptide (VIP), substance P (SubP), and galanin (GAL) in cultured sympathetic neurons. Therefore, we quantified NPY, VIP, SubP, and GAL mRNA in neurons of the stellate ganglia 1 week after ischemia-reperfusion to determine if neuropeptide expression was altered in cardiac sympathetic neurons. NPY, VIP, and SubP mRNAs were unchanged compared to unoperated control animals, but GAL mRNA was increased significantly. The increased GAL mRNA was not accompanied by elevated GAL peptide content in the stellate ganglia. Galanin content was increased significantly in the heart, however, indicating that elevated GAL mRNA led to increased peptide production. GAL content was increased in the left ventricle below the coronary artery ligation, but was not increased significantly in the atria or the base of the heart above the ligation. The buildup of GAL specifically in the damaged left ventricle is consistent with previous reports that GAL is transported to regenerating nerve endings after axon damage.
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PMID:Myocardial infarction stimulates galanin expression in cardiac sympathetic neurons. 1575 42

Many studies have shown that modulation of cytokine function is effective in ameliorating symptoms of rheumatoid arthritis. Neuropeptides have recently been shown to have powerful effects on the production and release of cytokines and have also been shown to exert potent proinflammatory and anti-inflammatory effects in animal models of inflammatory diseases. An analysis of cytokine and neuropeptide content of synovial fluid from patients with rheumatoid arthritis has revealed a significant correlation between two neuropeptides, bombesin/gastrin-releasing peptide and substance P, and the proinflammatory cytokine interleukin-6 as well as the erythrocyte sedimentation rate. These findings provide further evidence for a role of neuropeptides and cytokines in the pathophysiology of rheumatoid arthritis, as well as suggesting additional approaches for the development of novel therapeutic interventions.
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PMID:Gastrin-releasing peptide, substance P and cytokines in rheumatoid arthritis. 1589 28

Mast cells are critical players in allergic reactions, but they have also been shown to be important in immunity and recently also in inflammatory diseases, especially asthma. Migraines are episodic, typically unilateral, throbbing headaches that occur more frequently in patients with allergy and asthma implying involvement of meningeal and/or brain mast cells. These mast cells are located perivascularly, in close association with neurons especially in the dura, where they can be activated following trigeminal nerve, as well as cervical or sphenopalatine ganglion stimulation. Neuropeptides such as calcitonin gene-related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate cyclase activating peptide (PACAP), and substance P (SP) activate mast cells leading to secretion of vasoactive, pro-inflammatory, and neurosensitizing mediators, thereby contributing to migraine pathogenesis. Brain mast cells can also secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to corticotropin-releasing hormone (CRH), a mediator of stress which is known to precipitate or exacerbate migraines. A better understanding of brain mast cell activation in migraines would be useful and could lead to several points of prophylactic intervention.
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PMID:The role of mast cells in migraine pathophysiology. 1596 Sep 87

This study was conducted to identify bone resorption and anti-inflammatory effects with intermittent cyclical etidronate therapy (ICET) in patients with rheumatoid arthritis, and anti-inflammatory effect of etidronate in vitro. We compared bone mineral density (BMD), urinary deoxypyridinoline (DPD) level, bone alkaline phosphatase (BAP) level and Larsen damage scores between the ICET and the non-ICET groups for 3 years. The levels of interleukin-6 (IL-6), prostaglandin E2 (PGE2), substance P and vascular endothelial growth factor (VEGF) in synovial cells from arthritis models were measured following the addition of etidronate. In the ICET group, BMD and BAP levels increased. Urinary DPD level and the Larsen damage score were significantly lower than that in the non-ICET group. In the in vitro study, the production of IL-6, PGE2, substance P and VEGF were inhibited in a dose-dependent manner. Bone resorption and destruction inhibition effect of etidronate remained for 3 years. In vitro study showed that the production of inflammatory cytokines and an angiogenesis factor were inhibited.
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PMID:Inhibitory effect of bone resorption and inflammation with etidronate therapy in patients with rheumatoid arthritis for 3 years and in vitro assay in arthritis models. 1613 81

Aseptic loosening remains the primary cause of failure in total joint arthroplasty. Implant-derived particles are thought to be a main cause of osteolysis that leads to failure of total joint arthroplasty. The nervous system has been implicated in the etiology and pathogenesis of joint diseases. Substance P (SP) immunoreactive nerve fibers have been detected in the pseudomembrane and pseudocapsular tissues of aseptic loose hip prostheses, suggesting that SP might be involved in the process of aseptic loosening. Fibroblasts are abundant in periprosthetic membrane. Neuropeptides are able to modulate cytokine production by fibroblasts. In this study, we isolated fibroblasts from periprosthetic membrane at the time of revision hip arthroplasty performed because of aseptic loosening. Fibroblasts were stimulated with titanium (Ti) particles or SP. Prostaglandin (PG) E2 and interleukin-6 (IL-6) assays were performed using enzyme-linked immunosorbent assay kit. PGE2 and IL-6 secretion by fibroblasts have been significantly increased in the presence of Ti particles or SP. Moreover SP caused significant increase in PGE2 and IL-6 production by Ti particles-stimulated fibroblasts. Thus, SP and Ti particles acted synergistically to increase PGE2 and IL-6 secretion in fibroblasts from periprosthetic membrane.
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PMID:Substance P augments PGE2 and IL-6 production in titanium particles-stimulated fibroblasts from hip periprosthetic membrane. 1745 May 84

During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcepsilonRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34(+) progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-gamma (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte-macrophage colony-stimulating factor, but not IL-4, interferon-gamma or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases.
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PMID:Neuropeptides activate human mast cell degranulation and chemokine production. 1792 33

Conditions that influence the selective development or recruitment of connective tissue-type and mucosal-type mast cells (MCs) are not well understood. Here, we report that cynomolgus monkey embryonic stem (ES) cells cocultured with the murine aorta-gonad-mesonephros-derived stromal cell line AGM-S1 differentiated into cobblestone (CS)-like cells by day 10-15. When replated onto fresh AGM-S1 with the addition of stem cell factor, interleukin-6, and Flt3 ligand, these CS-like cells displayed robust growth and generated almost 100% tryptase/chymase double-positive MCs within 3 weeks. At all time points, the percentage of tryptase-positive cells did not exceed that of chymase-positive cells. These ES-derived MCs were CD45+/Kit+/CD31+/CD203c+/HLA-DR- and coexpressed a high-affinity IgE receptor on their surface, which was upregulated after IgE exposure. Electron microscopy showed that they contained many electron dense granules. Moreover, ES-derived MCs responded to stimulation by via IgE and substance P by releasing histamine. These results indicate that ES-derived MCs have the phenotype of functionally mature connective tissue-type MCs. The rapid maturation of ES-derived MCs suggests a unique embryonic pathway in primates for early development of connective tissue-type MCs, which may be independent from the developmental pathway of mucosal-type MCs.
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PMID:Direct development of functionally mature tryptase/chymase double-positive connective tissue-type mast cells from primate embryonic stem cells. 1799 16

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. Culture of sebocytes provides a new insight into the participation of neuropeptides, notably substance P (SP), in the pathophysiology of acne. To examine the possible involvement of neurogenic factors in the pathogenesis of acne, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), peroxisome proliferators activated receptors-gamma (PPAR-gamma) on the cultured sebocytes stimulated by SP. IL-1 is primarily proinflammatory cytokines to stimulate the expression of genes associated with inflammation. IL-6 is a pleiotropic cytokine with a wide range of biological activities and regulates inflammation. TNF-alpha is a pleiotropic pro-inflammatory cytokine that exerts multiple biologic effects. PPAR-gamma is a nuclear hormone receptor and plays a unique role in stimulating sebocyte lipogenesis. More numerous immunoreactivity to IL-1, IL-6, TNF-alpha and PPAR-gamma and increased RNA amplification for IL-1, IL-6, TNF-alpha and PPAR-gamma were observed after addition of SP compared with the control. This study reveals that SP is involved in the pathogenesis of acne.
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PMID:Influence of substance-P on cultured sebocytes. 1842 22

The etiology of esophageal mucosal injury is complex, since it may involve the reflux of gastric acid, bile acid, and pancreatic juice, external factors such as drugs and alcohol, or functional factors such as esophagogastric motility. The mechanism of esophageal mucosal injury has gradually been understood at the molecular biological level. It is particularly important that pro-inflammatory factors, such as inflammatory cytokines (interleukin-6 and -8), leukocytes and oxidative stress, have been demonstrated to be involved in the development of gastroesophageal reflux disease (GERD) including nonerosive reflux disease (NERD). In addition, nociceptors such as acid-sensitive vanilloid receptors, protease-activated receptors and substance P have also been implicated in the pathogenesis of neurogenic inflammation in NERD patients with esophageal hypersensitivity. The development of new therapy with anti-inflammatory and anti-oxidant effects is expected to assist in the treatment of intractable NERD/GERD and the prevention of carcinogenesis.
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PMID:Inflammation and oxidative stress in gastroesophageal reflux disease. 1843 9


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