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)

We studied the effect of vasoactive intestinal peptide (VIP), somatostatin (SOM), and substance P (SP) on IL-4-stimulated human IgE and IgG subclass production. VIP and SOM, but not SP, inhibited IgE production without affecting IgM or IgA production by mononuclear cells (MNC) from nonatopic donors from 10 pM to 10 nM. These neuropeptides also differentially modulated IgG subclass production. While IgG1 production was not affected by VIP, SOM, or SP, all of the neuropeptides enhanced IgG2 production. By contrast, SOM and SP, but not VIP, inhibited IgG3 production, whereas VIP and SP, but not SOM, enhanced IgG4 production. The effect by neuropeptides was specific since each peptide effect was specifically blocked by each antagonist. To achieve this effect, neuropeptides must be added at the start of the culture and be present throughout the entire culture period. The inhibition of IgE production was not mediated by known inhibitors of IgE production, IFN-gamma or PGE2, because the addition of anti-IFN-gamma mAb (10 micrograms/ml) or indomethacin (0.1 microM) did not overcome the inhibition of IgE production. In contrast to MNC, neuropeptides did not affect IgG subclass production in purified B cells. IgE production was not induced by IL-4 in purified B cells. Neuropeptides also failed to modulate IgG subclass production in cultures of B cells with either T cells or monocytes. However, they modulated IgE production and IgG subclass production in B cells in the presence of T cells and monocytes. In purified B cells, IL-4 plus anti-CD40 mAb induced IgE production which was not inhibited by VIP or SOM. However, VIP or SOM, but not SP, inhibited IgE production in B cells cultured with both T cells and monocytes. Finally, the mechanism of modulation of IgE and IgG4 production was dependent on IL-4-induced switching, since neuropeptides modulated IgG4 and IgE production in surface IgG4-negative (sIgG4-) and sIgE- B cells, respectively. In contrast, modulation of IgG2 and IgG3 production was not due to switching, since neuropeptides did not affect either IgG2 or IgG3 production in sIgG2- or sIgG3- B cells, respectively.
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PMID:Differential effect of vasoactive intestinal peptide, somatostatin, and substance P on human IgE and IgG subclass production. 138 70

Neuropeptides can influence immune effector cell function at both systemic and mucosal immune sites. We examined the ability of substance P (SP) to modulate the natural killer (NK) activity of intestinal intraepithelial leucocytes (IEL). Yac-1 killing by IEL but not splenic cells was increased after either 18 hr preincubation or 6 hr of co-incubation with SP. We also examined the NK activity of IEL and spleen isolated from mice treated with SP in vivo. The selective increase in NK activity of IEL occurred without any demonstrable change in the number or phenotype of the IEL. The IEL responsive to SP in vivo and induced in vivo by SP were both Thy-1- and did not kill the NK insensitive mastocytoma cell line P815. Lastly, we examined the ability of SP to induce the release of interleukin-2 (IL-2) and IL-4 from IEL after 6 and 18 hr of in vitro culture. No increase in the release of these cytokines was observed, suggesting that IL-2 and IL4 are not involved in the local augmentation of IEL NK activity by SP. These observations suggest that SP has a selective stimulatory effect on intestinal activity and may play a role in the regulation of intestinal cell-mediated immunity.
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PMID:Selective modulation of the natural killer activity of murine intestinal intraepithelial leucocytes by the neuropeptide substance P. 169 80

The presence of adrenocorticotropic hormone (ACTH) and substance P (SP) receptors on leukocytes is suggestive that these cells can respond to these ligands. To address this possibility, we have investigated the consequences of ACTH and SP stimulation of B cells. As a result, enhanced immunoglobulin synthesis mimicking an IL-4-like mechanism was noted. Importantly, this stimulation could be induced at ligand concentrations at or near the kD for their receptors. Herein these effects by ACTH and SP were described using B cell lymphoma cell lines and normal B cells.
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PMID:The regulation of antibody responses by mini-cytokines. 172 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.
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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

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.
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PMID:Substance P selectively activates TNF-alpha gene expression in murine mast cells. 768 20

The effect of vasoactive intestinal peptide (VIP), somatostatin (SOM), and substance P (SP) on spontaneous human IgE and IgG4 production in atopic patients was studied. In cultures of mononuclear cells (MNC), VIP inhibited both IgE and IgG4 production without affecting IgM, IgA, IgG1, IgG2, or IgG3 production. In contrast, SOM inhibited only IgE production whereas SP inhibited only IgG4 production without affecting production of other isotypes or other IgG subclasses. The effect of neuropeptides was specific because each was specifically blocked by a corresponding neuropeptide antagonist. To achieve the effect noted above, neuropeptides must be added at the start of the culture. IFN-alpha and IFN-gamma were found to inhibit both IgE and IgG4 production whereas prostaglandin E2 (PGE2) inhibited only IgE production. However, the inhibition of IgE and IgG4 production by neuropeptides could not have been mediated by IFN-alpha, IFN-gamma, or PGE2 because the addition of anti-IFN-alpha, anti-IFN-gamma, and indomethacin, respectively, did not reverse the inhibition. In contrast to their effects on MNC, neuropeptides did not affect production of either IgE or IgG4 by purified B cells; the addition of either T cells or monocytes to B cells had no effect on this. However, neuropeptides were effective in inhibiting IgE and IgG4 production by B cells cultured together with both T cells and monocytes. Depletion of sIgE+ and sIgG4+ B cells resulted in abrogation of IgE and IgG4 production, respectively. However, stimulation of sIgE- B cells with IL-4 plus anti-CD 40 mAb induced IgE production, which was inhibited by VIP and SOM, but not SP, in the presence of both T cells and monocytes. These results suggest that neuropeptides inhibited spontaneous IgE and IgG4 production by interaction with sIgE+ and sIgG4+ B cells in a T cell- and monocyte-dependent fashion. In addition, VIP and SOM also inhibited IgE production by modulating switching induced by IL-4 plus anti-CD 40 mAb in a T cell- and monocyte-dependent fashion.
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PMID:Effect of vasoactive intestinal peptide, somatostatin, and substance P on spontaneous IgE and IgG4 production in atopic patients. 768 25

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

Light chain gene rearrangement during mammalian pre-B differentiation generally occurs in an orderly manner, beginning with kappa genes and proceeding through lambda genes. We have previously shown that human pre-B cell differentiation in vitro leads to a skewing toward lambda expression, resulting in a higher percentage of lambda+ cells than kappa+ cells. We now report that the multifunctional polypeptide transforming growth factor-beta (TGF-beta) exerts a selective inhibitory effect on the acquisition of cell surface lambda light chains during in vitro differentiation of normal human pre-B cells, giving rise to a balanced ratio (approximately 1:1) of kappa+ to lambda+ cells that resembles what normally exists in vivo. The TGF-beta effect was ablated using a neutralizing anti-TGF-beta antiserum and TGF-beta had no significant effect on the acquisition of kappa or surrogate light chains. Experiments using highly enriched pre-B cells (90-95% cytoplasmic mu+) suggested that the TGF-beta effect was directly on the pre-B cell or the pre-B cell to mu+/lambda+ immature B cell transition. The following peptides, cytokines, and antibodies had no effect on light chain acquisition or expression: substance P, vasoactive intestinal peptide, leu/met enkephalin, IL-1, IL-4, IL-7, anti-class II MHC, anti-CD24, anti-CD40, and the CD10 inhibitor phosphoramidon. A selective regulatory role for TGF-beta on normal human B cell development in the bone marrow microenvironment is suggested by these results.
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PMID:Transforming growth factor-beta regulates normal human pre-B cell differentiation. 815 4

Phospholipase C-mediated release of inositol trisphosphate, followed by an increase in free intracellular calcium, is an important signal transduction pathway for several membrane receptors. In the present investigation, the coupling of various receptors to phospholipase C was studied in the human keratinocyte line HaCaT. Inositol trisphosphate formation was determined by anion-exchange chromatography, and the release of intracellular calcium was analysed with the fluorescence probe Fura-2 AM. Activation of HaCaT keratinocytes with bradykinin resulted in a time- and dose-dependent release of inositol trisphosphate and intracellular calcium, with an EC50 value of 50 nM for bradykinin-induced inositol trisphosphate formation. The mediators and cytokines IL-1, IL-4, IL-6, IL-8, EGF and TGF alpha, as well as bombesin, prolactin, carbachol, substance P and retinoic acid, did not activate this pathway. The inability of the mediators examined to activate phospholipase C may be due to lack of the respective cognate receptors or to the use of other signal transduction pathways.
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PMID:Inositol phosphate formation and release of intracellular free calcium by bradykinin in HaCaT keratinocytes. 830 79


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