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)

The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy.
 ...
PMID:Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists. 149 61

Neurodegenerative processes in Alzheimer disease (AD) are thought to be driven in part by the deposition of amyloid beta (A beta), a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Recent descriptions of in vitro neurotoxic effects of A beta support this hypothesis and suggest toxicity might be mediated by A beta-induced neuronal calcium disregulation. In addition, it has been reported that "aging" A beta results in increased toxic potency due to peptide aggregation and formation of a beta-sheet secondary structure. In addition, A beta might also promote neuropathology indirectly by activating immune/inflammatory pathways in affected areas of the brain (e.g., cortex and hippocampus). Here we report that A beta can modulate cytokine secretion [interleukins 6 and 8 (IL-6 and IL-8)] from human astrocytoma cells (U-373 MG). Freshly prepared and aged A beta modestly stimulated IL-6 and IL-8 secretion from U-373 MG cells. However, in the presence of interleukin-1 beta (IL-1 beta), aged, but not fresh, A beta markedly potentiated (3- to 8-fold) cytokine release. In contrast, aged A beta did not potentiate substance P (NK-1)- or histamine (H1)-stimulated cytokine production. Further studies showed that IL-1 beta-induced cytokine release was potentiated by A beta-(25-35), while A beta-(1-16) was inactive. Calcium disregulation may be responsible for the effects of A beta on cytokine production, since the calcium ionophore A23187 similarly potentiated IL-1 beta-induced cytokine secretion and EGTA treatment blocked either A beta or A23187 activity. Thus, chronic neurodegeneration in AD-affected brain regions may be mediated in part by the ability of A beta to exacerbate inflammatory pathways in a conformation-dependent manner.
 ...
PMID:Amyloid beta peptide potentiates cytokine secretion by interleukin-1 beta-activated human astrocytoma cells. 747 75

The immune cytokine interleukin-1 (IL-1) causes a pronounced elevation in substance P (SP) immunoreactivity and the mRNA coding for its preprotachykinin precursor in cultured superior cervical (sympathetic) ganglia (SCG; Jonakait and Schotland, 1990; Freidin and Kessler, 1991; Hart et al., 1991). In this study we have investigated the possibility that the SCG can respond to other immune stimulators, notably lipopolysaccharide (LPS), a product of bacterial cell walls. LPS treatment of cultured SCG resulted in a dose-dependent increase in SP. However, LPS did not induce SP in the absence of non-neuronal cells, suggesting the necessity of a non-neuronal cell-derived intermediate. Since the LPS induction of SP was partially blocked by a specific IL-1 receptor antagonist (IL-1ra) and since LPS induced approximately an 8-fold increase in mRNA coding for IL-1 itself, we concluded that IL-1 is at least one of these LPS-induced intermediates. TNF-alpha, which also raises SP levels, may be another. IL-6, which may also be increased by LPS, does not increase levels of SP. The synthetic glucocorticoid hormone dexamethasone (DEX) blocks the LPS induction of SP with a Ki approximating 8 x 10(-11) M. The inhibition is due in part to the blockade of the LPS induction of ganglionic IL-1 mRNA. Moreover, inhibition of the LPS induction of SP by indomethacin implies mediation of the effect through prostaglandins. The inhibition by indomethacin suggests a non-monocytic cell source since prostaglandins are thought to restrict the LPS induction of monocytic IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lipopolysaccharide induces substance P in sympathetic ganglia via ganglionic interleukin-1 production. 750 97

Macrophages are supposed to play a key role in inflammatory and tumor angiogenesis. Their importance derives from (1) their ubiquitous presence in normal and especially inflamed tissues, (2) their potential to become activated in response to appropriate stimuli, and (3) their repertoire of secretory products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF-I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha, substance P, prostaglandins, interferons, thrombospondin 1), activated macrophages have the capability to influence each phase of the angiogenic process, such as alterations of the local extracellular matrix, induction of endothelial cells to migrate or proliferate, and inhibition of vascular growth with formation of differentiated capillaries. This review describes macrophage physiology and the influence of macrophage secretory products on the different phases of angiogenesis in vitro and in vivo.
 ...
PMID:Macrophages and angiogenesis. 750 44

New rod photoreceptors are added to mature teleost retinas throughout life by regulated proliferation of rod precursor cells (RPCs). In this study, candidate regulators of RPC proliferation, acidic and basic fibroblast growth factors (aFGF and bFGF; 0.1 microgram/eye), interleukin-6 (IL-6; 0.1 microgram) and phytohaemagglutinin (HA15; 1.0 microgram), were injected intravitreally into one eye of goldfish (body length 5-6 cm), and mitotic RPCs in both retinas were detected and counted 3-50 days later by immunohistochemistry for proliferating cell nuclear antigen (PCNA). Retinal integrity after treatment was assessed by immunohistochemistry for tyrosine hydroxylase (TH) and other retinal antigens. All the agents applied altered the density of PCNA-immunoreactive (ir) cells in the outer and inner nuclear layers (ONL and INL) in both retinas as soon as 2-3 days after unilateral injection. Initially (2-20 days after injection), particularly in the treated retina, PCNA-ir cells appeared in clusters accompanied by various numbers of scattered individual cells, but subsequently the clusters of PCNA-ir cells disappeared while the density of singly distributed cells increased until 30 days after injection. At the doses given, these effects were most striking with aFGF and bFGF and less with IL-6 and HA15. In radial cryosections, other cellular elements immunoreactive to markers such as TH, serotonin, neuropeptide Y, substance P, glutamine synthetase, glial fibrillary acidic protein and protein kinase C, were found normal in terms of morphology. In addition, a monoclonal antibody (NN-2) was found to label some non-neuronal structures (macrophages, microglia and blood vessels) inside and outside the retina intoxicated with 6-hydroxydopamine, a few NN-2-ir cells being PCNA-positive. However, clustered PCNA-ir and marginal neuroblast cells were NN-2-negative. These results indicate that FGFs may play an important role in stimulating the proliferation of RPCs, for example, in the regeneration of fish retinas following neurotoxic destruction.
 ...
PMID:Fibroblast growth factor induces proliferating cell nuclear antigen-immunoreactive cells in goldfish retina. 751 Mar 76

Experimental data strongly suggest that the nervous and immune systems are interrelated. One example of this interrelation is anatomical and is represented by innervation of the lymphoid organs by substance P (SP) immunoreactive fibers, among others. Neurotransmitters/neuropeptides can exert functional receptor-mediated immunologic responses. SP binding to its receptor induces cytokine production in macrophages and T cells and stimulates IgG secretion from B cells. SP has also been associated with inflammation and other immune-mediated diseases such as arthritis. We have previously reported an in vitro stimulatory effect of SP on hematopoiesis that was mediated mostly by the induction of two relevant hematopoietic growth factors, IL-3 and granulocyte-macrophage-CSF (GM-CSF). In this study, we have shown that SP, through the carboxyl terminus, induces the production of IL-3 and GM-CSF in bone marrow mononuclear cells. This production requires de novo synthesis and is blocked by two different SP-R antagonists, spantide and CP-96,345-1. The induction of IL-3 and GM-CSF is partially mediated by IL-1 and IL-6, which are also produced by bone marrow mononuclear cells. Furthermore, the production of IL-3 and GM-CSF correlated with an accumulation of their respective steady state mRNAs. T cells found within the bone marrow are responsible for most of the induced IL-3. Because SP mediates the release of IL-1, IL-3, IL-6, and GM-CSF, all important hematopoietic regulators, by bone marrow cells, this study further suggests the possibility of a regulatory role of the nervous system in hematopoiesis mediated by neuropeptides such as SP.
 ...
PMID:Induction of IL-3 and granulocyte-macrophage colony-stimulating factor by substance P in bone marrow cells is partially mediated through the release of IL-1 and IL-6. 751 64

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.
 ...
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.
 ...
PMID:Induction of IgA1 and IgA2 production in immature human fetal B cells and pre-B cells by vasoactive intestinal peptide. 753 91

The neuropeptide Substance P (SP) is widely distributed in the peripheral nervous system. Its biologic effects have been extensively studied in the immune system. However, even though the bone marrow (BM) is innervated with SP-immunoreactive fibers and some of its cells not only express SP receptors (T and B cells, endothelial cells, and macrophages) but also produce SP (macrophages, eosinophils, and endothelial cells), the effects of SP on hematopoiesis are scanty. Furthermore, SP induces the production of hematopoietic growth factors (HGFs) (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) from human monocytes. In this study, we have found a potent in vitro stimulatory effect of SP (10(-8) to 10(-12) mol/L) on hematopoiesis for both erythroid and granulocytic progenitors in short-term methyl-cellulose BM cultures. SP alone, in the absence of exogenous HGFs, is able to sustain hematopoiesis in vitro. This stimulatory effect of SP is: (1) mostly mediated by the adherent cells; (2) completely abrogated by two SP receptor (SP-R) antagonists; and (3) partially reduced by anti-IL-1, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, it appears that the stimulatory effect of SP may be mediated by IL-3 and GM-CSF because we have also found that SP induces the release of these two cytokines from BM mononuclear cells. Considering that the SP effect occurs at concentrations as low as 10(-11) mol/L, and via a specific receptor, it appears that SP may play a physiologic role in regulating hematopoiesis, at least partially through the adherent BM cells and the release of HGFs, and may place SP, a neuropeptide, in a new category of hematopoietic regulators.
 ...
PMID:In vitro stimulatory effect of substance P on hematopoiesis. 767 16

There is increasing evidence that the neurologic system is capable of modulating a wide range of immunologic responses, including certain inflammatory processes in the lung, gastrointestinal tract, and skin. It has been proposed that secreted neuropeptides such as substance P (SP) may mediate these neuroinflammatory interactions by binding to and stimulating immune cells such as mast cells and lymphoid cells. SP is secreted in a variety of tissues by an extensive network of neurosensory C and A5 fibers in response to a wide range of noxious stimuli and injury. Previous studies to examine the effect of SP on mast cells have focused on its role in triggering histamine release and mediating immediate hypersensitivity responses. Recently it was demonstrated that mast cells are also capable of secreting multiple cytokines including TNF-alpha, IL-1, IL-3, IL-4, IL-6, and GM-CSF. In this study we tested the possibility that SP may also influence mast cell-mediated late inflammatory events by modulating the production of one or several of these cytokines. Our results indicate that SP induces TNF-alpha mRNA expression and TNF-alpha secretion in a dose-dependent manner in a murine mast cell line, CFTL12. Likewise, SP stimulates TNF-alpha secretion in freshly isolated murine peritoneal mast cells. The induction of mast cell TNF-alpha is selective, since SP does not stimulate the production of IL-1, IL-3, IL-4, IL-6, or GM-CSF in these cells. The CFTL 12 mast cell line constitutively expresses high levels of SP receptor mRNA which is not modulated by PMA/cycloheximide treatment or SP. These results further support the concept that the neurologic system modulates inflammatory events by neuropeptide-mediated mast cell cytokine release.
 ...
PMID:Substance P selectively activates TNF-alpha gene expression in murine mast cells. 768 20


1 2 3 4 5 6 7 8 9 10 Next >>