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) and Somatostatin (SOM), so as other neuropeptides can modulate neurologic and immunologic functions. sP has been described to enhance both in vitro and in vivo immunoglobulin synthesis. On the contrary, SOM has an inhibitory effect on the same activity. The modulating effect is more evident on IgA isotype. Hypergammaglobulinemia and in particular high levels of IgA is a common finding in pediatric AIDS and an imbalance among regulatory effects of neuropeptides might be suggested. In order to evaluate the plasma levels of sP in pediatric AIDS we studied 15 children with HIV infection (status P2), 10 seronegative children born to HIV positive mothers and 10 healthy children of the same age. All the HIV positive children had high plasma levels of IgG and IgA. The plasma level of sP was extremely higher in HIV positive children while no significant difference was found between seronegative children born to HIV positive mothers and healthy children. SOM was decreased in HIV positive children when compared to control groups but a significant difference was not reached. It might be supposed that HIV infection, through a dysregulation among neuropeptides interferes on immune functions and in particular on IgA synthesis. On the other hand it might be suggested that the imbalance between sP and SOM depends on the viral infection of immune cells since it has been demonstrated that SOM and other neuropeptide are synthesized by lymphoid tissue. Further studied relevance of neuropeptide disorders in pediatric AIDS.
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PMID:[Changed levels of substance P and somatostatin in HIV-positive children]. 128 55

The effect of vasoactive intestinal peptide (VIP) on human lymphoblastoid B cell lines and tonsil B cells was studied. VIP increased immunoglobulin production and proliferation by lymphoblastoid B cell line, GM-1056, in a dose-dependent manner. As little as 10(-12) M of VIP was effective, and higher concentrations of VIP induced an approximately five-fold increase in IgA production. Moreover, this enhancement was blocked by VIP antagonist. Similarly, VIP enhanced IgM and IgG production by other lymphoblastoid B cell lines, CBL and IM-9, respectively. In contrast to VIP, another neuropeptide substance P (SP) or somatostatin failed to enhance immunoglobulin production and thymidine uptake. VIP also enhanced IgA production and thymidine uptake by purified tonsil B cells. However, in contrast to B cell lines, VIP failed to enhance IgM and IgG production by tonsil B cells. SP or somatostatin failed to enhance immunoglobulin production or thymidine uptake by tonsil B cells. These results indicate that VIP acts as B cell stimulatory factor and that VIP may also have preferential effect on IgA production on tonsil B cells.
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PMID:Vasoactive intestinal peptide stimulates immunoglobulin production and growth of human B cells. 131 95

B cells respond to a variety of effector molecules that can induce these cells to differentiate. One such molecule is the neuropeptide, substance P (SP). Previous studies have demonstrated the presence of SP receptors on lymphocytes while limited studies have been able to demonstrate the biological significance of their expression. SP has been shown to enhance IgA and IgM responses by Peyer's patch and splenic B cells. A limitation of these studies was that the direct effect of SP upon B cells was not ascertained, suggesting these B cells were stimulated via alternate mechanisms. To this end, evidence here will be discussed that SP can directly interact with clonal B lymphoma cells and highly purified splenic B cells. The data implicate SP as a late-acting B cell differentiation factor that requires an additional triggering mechanism to initiate the B cell differentiation process.
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PMID:The cytokine-like action of substance P upon B cell differentiation. 138 Feb 78

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

The interaction between the nervous system, immune system and bronchial reactivity was studied in rats by using the neurotoxin capsaicin. Rats were treated with capsaicin at 1-2 days of age or at adult age, before or after sensitization by subcutaneous injections with ovalbumin (OA). The levels of the neuropeptides neurokinin A and calcitonin gene-related peptide were decreased in the lung after capsaicin treatment, as determined with radioimmunoassay, whereas the levels of neuropeptide Y were unaffected. The levels of IgA, IgE and IgG in bronchial lavage were also affected by capsaicin treatment; however, the results were heterogeneous. Capsaicin treatment after sensitization reduced the bronchial reactivity to challenge with OA aerosol and serotonin iv. The results demonstrated that reduction of neuropeptide levels with capsaicin affected both bronchial reactivity and the levels of antibodies in bronchial lavage fluid. However, no correlation between these two parameters was seen, demonstrating the complexity of the system.
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PMID:Local immune response and bronchial reactivity in rats after capsaicin treatment. 165 49

Recently, we have demonstrated a substance P (SP)-dependent modulation of in vitro IgM and interferon-gamma (IFN-gamma) secretion by human peripheral blood mononuclear cells, as well as lymphokine activities in supernatants of cultured duodenal mucosa. Therefore we investigated other local immunoregulatory effects of SP. Duodenal biopsies of 7 healthy subjects were cultured with Pokeweed mitogen (PWM, 1 microgram/ml) for 4 days at 37 degrees C in 1 ml medium each. SP was added in concentrations ranging from 10(-12)M to 10(-6)M on day 1. Fresh media with fresh PWM were added every day. IgG, IgM, IgA (ELISA) and IFN-gamma (RIA) were determined in the culture supernatants. Values were referred to 5 mg biopsy weight and expressed as % change in basal PWM pulsed secretion, or as units/ml. 10(-6) M and 10(-12) M SP increased secretion of all immunoglobulin isotypes. Compared to controls, 10(-6) M and 10(-12) M SP led to an increase in IgM secretion of up to 73 +/- 23% and 41 +/- 32% and to an increase in IgA secretion up to 96 +/- 35% and 25 +/- 33%, respectively (alpha = 0.02 for both isotypes at 10(-6) M). 10(-12) M to 10(-6) M SP led to a significant dose-dependent increase in IFN-gamma secretion from 7.08 +/- 1.65 up to 21.8 +/- 12.6 units/ml/5 mg. The maximum effect could be seen on culture days 3 and 4. We were able to demonstrate for the first time that SP stimulates PWM pulsed immunoglobulin and IFN-gamma secretion by human duodenal immunocompetent cells. These results support the hypothesis of local neuropeptidergic-immune interactions.
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PMID:Effect of substance P on immunoglobulin and interferon-gamma secretion by cultured human duodenal mucosa. 168 96

The IgA producing murine B lymphoma, CH12.LX.C4.4F10 (4F10) and the IgM producing murine lymphoma, CH12.LX.C4.5F5 (5F5) were found to express substantial numbers of substance P (SP) receptors having dissociation constants equal to 0.69 nM. Binding of SP by these B lymphoma cells was via the tachykinin-specific C-terminus sequence, Phe-X-Gly-Leu-Met-NH2, because SP, SP antagonist (D-Pro2-D-Phe7-D-Trp9-SP), eledoisin, and substance K could effectively inhibit radiolabeled SP binding, whereas the SP N-terminus fragment, SP (1-4), could not. The functionality of these receptors could be demonstrated by the ability of subnanomolar concentrations of SP to induce Ig secretion in a dose-dependent fashion. However, the presence of a second stimulus in these cultures was required to obtain maximal increases. IgA secretion by 4F10 cells was elevated only 25 to 37%, and IgM secretion by 5F5 cells was not significantly increased in cultures in which nanomolar concentrations of SP were present. Conversely, coculturing 5F5 cells with a suboptimal concentration of LPS (50 ng/ml) and 10(-10)M SP resulted in an approximate threefold increase in supernatant IgM when compared to control cultures stimulated with LPS alone. While not as dramatic, 10(-10) M SP also enhanced IgA secretion of LPS-stimulated 4F10 cells by approximately 45%. This enhancement of Ig secretion was SP-specific, as evidenced by the ability of 1000-fold excess of SP antagonist to block SP-induced, but not LPS-induced, Ig production. Clearly, SP could act synergistically with LPS to enhance Ig secretion; therefore, we questioned whether this augmentation was also reflected at the level of H chain mRNA expression. 10(-9)M SP induced modest increases (50 to 60%) in mu-chain mRNA expression by LPS-stimulated 5F5 cells when compared with cells stimulated with LPS alone. The 4F10 cells did not display this magnitude of difference for alpha-chain mRNA expression. Thus, although SP-induced increases of mu-chain mRNA by 5F5 cells may contribute to the increased Ig secretion observed by these LPS-activated lymphocytes, it is unlikely that increased mRNA expression can totally account for the threefold increases in secretion that were observed.
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PMID:Substance P acts directly upon cloned B lymphoma cells to enhance IgA and IgM production. 170 87

The sources of different chemical substances in the NF of allergic patient, such as albumin, secretory IgA, histamine, leukotriene, kinin and substance P were investigated. To accomplish this, we challenged the inferior turbinate on one side, but separately collected NF from both sides in patients with nasal allergy to house-dust. Provocation was done with paper disc containing dried allergen extract. Collection was done by suction for the first five minutes immediately after the onset of a positive response to nasal provocation. The total amount of the chemical substances on each side was analyzed separately and compared. Significant differences were seen between both sides only for histamine and leukotriene. In consideration with the previous reports, it is suggested that in nasal allergen challenge the major sources are glandular secretion for secretory IgA, and albumin, and secretion for migrating cells for histamine and leukotriene. The major sources responsible for kinin and substance P, however, are not defined.
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PMID:The sources of chemical substances in allergic nasal fluid. 171 74

Murine B cells have been shown to possess substance P (SP) receptors, but their functional and biological significance remains unresolved. While previous studies have suggested that SP can induce B cells to secrete Ig, the effect could be indirect since mixed cultures were used. In order to assess directly the ability of SP to trigger normal B cells, we have studied the effects of this neuropeptide on purified splenic B cells in vitro. Although an activation, e.g. lipopolysaccharide (LPS), was required, the functionality of the B cell SP receptors was clearly shown by the ability of subnanomolar concentrations of this neuropeptide to augment antibody secretion in a dose-dependent fashion. Specifically, IgM and IgG levels, determined by an isotype-specific sandwich ELISA, were greatly enhanced at 10(-10) M SP by as much as 500 and 572% respectively, while IgA levels were only modestly affected. Even picomolar concentrations of SP could significantly increase IgM levels. This observed enhancement of Ig production was SP specific since B cells co-cultured in the presence of excess SP antagonist were reduced to basal LPS-stimulated Ig levels. Furthermore, this synergistic stimulation by SP and LPS upon normal B cells could not be attributed to SP-induced cell proliferation since stimulatory concentrations of SP were not mitogenic and at high concentrations could inhibit cell proliferation. Rather, it was observed that the increased IgM and IgG secretion was in part attributable to a greater number of B cells secreting antibodies as demonstrated with an ELISPOT assay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroimmune modulation of lymphocyte function--I. Substance P enhances immunoglobulin synthesis in lipopolysaccharide activated murine splenic B cell cultures. 172 93

We examined the effect of vasoactive intestinal peptide, substance P, and somatostatin on concanavalin A (1 microgram/ml)-induced lymphocyte proliferation and immunoglobulin (IgA, IgM, and IgG) synthesis by cells from spleens, Peyer's patches, and mesenteric lymph nodes. These neuropeptides (10(-7) to 10(-12) M) modulated immune responses in a dose-dependent manner. For a comparative study, neuropeptides were used at 10(-8) M concentration. Both vasoactive intestinal peptide and somatostatin significantly decreased DNA synthesis (30 to 50%), whereas substance P increased synthesis (40%) in lymphocytes from all organs tested. IgA synthesis was significantly altered by all of the neuropeptides tested, whereas IgM synthesis was less affected and IgG synthesis was virtually unchanged. Somatostatin inhibited IgA (20 to 50%) and IgM (10 to 30%) synthesis in lymphocytes from all three organs. Substance P increased IgA synthesis in mesenteric lymph nodes (50%), spleens (70%), and Peyer's patches (300%). It also increased IgM synthesis in Peyer's patches (20%) and spleens (30%), but was without effect on IgM synthesis in mesenteric lymph nodes. Vasoactive intestinal peptide increased the IgA response in mesenteric lymph nodes (20%) and spleens (30%), but inhibited IgA synthesis in lymphocytes from Peyer's patches (60%). Interestingly, in Peyer's patches, IgM synthesis was increased by vasoactive intestinal peptide (80%), whereas it was unchanged in mesenteric lymph nodes and spleen. Thus, not only did these neuropeptides have different effects on the production of different immunoglobulin isotypes, but their effect was also organ-specific. Because neuropeptides which are abundant in the intestine can modulate IgA and other immunoglobulin synthesis in vitro, they may play a significant regulatory role in mucosal immune responses in vivo.
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PMID:Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. 241 14


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