UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 micrograms acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization 'shutdown' period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involvement of substance P as a major mediator of immunological memory.
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PMID:Substance P increases and prolongs increased output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo: is it a mediator of immunological memory? 170 49

In birds, B-lymphocytes mature in a special immune organ, the Bursa Fabricii. This organ thus offers unique possibilities for the study of the microenvironment of B-lymphocyte differentiation. We previously reported tachykinin-, vasoactive intestinal peptide-, calcitonin gene-related peptide- and galanin-immunoreactive (ir) fibres in the chicken bursa. As judged from light microscopic studies, each of the peptides was found in fibres contacting B-lymphocytes. Vasoactive intestinal peptide-ir fibres contacted macrophages. Now, we demonstrate neuropeptide Y, indicating the sympathetic nervous system, in fibres associated with arteries, not entering the follicles. CD4- and CD8-positive T-lymphocytes were dispersed in bursal follicles and the connective tissue, most densely in subepithelial regions. We could not find close apposition of fibres with either T-cell subset. We conclude that the potential neuro-immune axis in the Bursa Fabricii may represent a neuro-B-cell-link with only indirect participation of T-lymphocytes. The sympathetic input may influence the bursal microenvironment primarily by regulating the blood supply.
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PMID:Peptidergic innervation of the Bursa Fabricii: interrelation with T-lymphocyte subsets. 177 37

The embryo expresses paternal antigens foreign to the mother and therefore has been viewed as an allograft. The maternal immune system responds to paternal antigens on the "graft", and these responses are thought to protect pregnancy. However, pregnancy can be aborted by stress, which stimulates local production of TNF-alpha and inhibits TGF-beta 2-producing natural suppressor cell (NS) activity via a neurotransmitter substance P-dependent pathway. Immunization protects against stress-triggered abortion and CD8+ T cells appear to be required. The objective of the present study was to investigate the importance of CD8+ T cells in the prevention of stress-triggered abortion by immunization. Injection of anti-CD8 increased the abortion rate in nonimmunized mice and in immunized mice. Following anti-CD8 injection, stress failed to further increase the abortion rate; a similar high rate of abortion was seen in immunized and anti-CD8-injected mice. These data suggested that stress could act by neutralization and/or elimination of immunoprotective CD8+ T cell function. CD8+ T cells from pregnant mice have been reported to produce a 34-kDa suppressor factor, but we detected a 1.5- to 2-kDa suppressive factor in the HPLC fractions of supernatants obtained from nonstressed decidua, and this activity was abolished by stress and boosted by immunization with Balb/c cells.
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PMID:Inhibition of immunoprotective CD8+ T cells as a basis for stress-triggered substance P-mediated abortion in mice. 880 91

Substance P has various immunomodulatory effects, including in vitro modification of lymphocyte proliferation and cytokine release. Elevated levels of substance P and increased staining of substance P-positive nerve fibres have been reported in atopic dermatitis patients. We examined fluoresceinated substance P binding to a range of lymphocyte subsets and compared the results in atopic dermatitis, non-atopic psoriasis patients and normal controls. Fluoresceinated substance P and phycoerythrin-labelled monoclonal antibodies to CD3, CD4, CD8, CD57, CD19 and CD14 were incubated in duplicate with Ficoll-Hypaque separated peripheral blood mononuclear leukocytes. With flow cytometry the fluoresceinated substance P-positive cells were identifiable as a peak of positively fluorescent cells, and the percentages of positive cells were measured. We have demonstrated binding of fluoresceinated substance P to all subsets examined, with significantly less binding to atopic dermatitis CD3-, CD8- and CD57-positive cells. This may affect cytokine release and hence be important in the pathogenesis of atopic dermatitis.
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PMID:Substance P binding to peripheral blood mononuclear leukocytes in atopic dermatitis. 922 14

Reciprocal communication between the immune system and the neuroendocrine system is mediated via a common chemical language of shared ligands and receptors. The neuropeptide substance P (SP) has been implicated as a mediator of immunomodulation. The evidence for substance P receptors on human lymphocytes is, however, controversial. The aims of the present study are to investigate substance P receptor (SPR) expression in human peripheral and mucosal mononuclear cells and to identify cellular sites of expression in human colonic mucosa. Using reverse-transcriptase PCR, we demonstrate that PBMC isolations are negative for SPR mRNA expression, whereas lamina propria mononuclear cell (LPMC) isolations express on average eight SPR mRNA transcripts per cell. In situ hybridization performed on surgically resected colonic tissue confirms the expression of SPR mRNA in LPMC in vivo. SPR mRNA signal was detected in LPMC, lymphoid follicles, and epithelium. The complementary technique of immunohistochemistry gave a similar distribution of SPR expression that colocalized with CD45 immunoreactivity. Dual-fluorochrome flow cytometry revealed SPR expression by CD4, CD45RO, CD45RA, CD8, CD19, and CD14 LPMC subsets, but not PBMC. Our findings suggest that SPR expression is distinctive of human colonic mucosal mononuclear cells and support a direct role for SP in mucosal immunomodulation.
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PMID:Substance P (neurokinin-1) receptor is a marker of human mucosal but not peripheral mononuclear cells: molecular quantitation and localization. 972 16

Substance P (SP), one of the most prevalent neuropeptides in gut, has been reported to have potent immune modulatory effects as a proinflammatory agent. The synthesis of SP and SP receptor expression in intraepithelial and lamina propria T lymphocytes of mouse intestine was investigated. Using RT-PCR analysis, it was demonstrated that SP receptor mRNA was exclusively expressed in intraepithelial and lamina propria T lymphocytes as well as their purified CD4+, CD8+ and CD4-CD8-CD3+ subsets. Messenger RNAs (mRNAs) for the two precursors of SP, beta and gamma-preprotachykinin-A, were also detected. These results were consistent in lymphocytes from both epithelium and lamina propria of small and large intestines, although the frequencies and/or intensities of mRNA expression varied. However, none of the findings could be repeated in splenic T lymphocytes. Activation of splenocytes with anti-CD3epsilon-chain mAb and PMA did not induce expression of SP or its receptor mRNAs. Furthermore, both cytoplasmic and surface-bound SP was demonstrated in intestinal T lymphocytes using dual color immunocytochemistry and immunoflow cytometry. In vitro treatment with SP did not significantly change the size of the SP-immunoreactive T cell population, indicating the presence of SP receptor on intestinal T lymphocytes as well as in vivo binding of endogenously released SP. Our data suggest that SP production and SP receptor expression are distinctive for mouse intestinal mucosal immunity and that SP may act as a modulator of an ongoing controlled inflammation in normal gut, by acting through its specific receptor on T lymphocytes in an autocrine and/or paracrine pattern.
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PMID:Both substance P and its receptor are expressed in mouse intestinal T lymphocytes. 1139 9

Hemokinin 1 (HK-1) is a new member of the tachykinin peptide family that is expressed in hematopoietic cells. Recent reports studying mouse, rat, and human orthologs of HK-1 demonstrate a broader distribution than originally reported. Our previous studies demonstrated that HK-1, by promoting proliferation, survival, and possibly maturation of B-cell precursors, plays an important role in B lymphopoiesis. Here we present data showing that HK-1 also influences T-cell development at a similar stage of differentiation. This peptide enhanced the proliferation of T-cell precursors and increased the number of thymocytes in fetal thymus organ cultures (FTOCs). Tachykinin antagonists, on the other hand, greatly reduced the cellularity of thymi both in vivo and in vitro. The major reduction occurred in the CD4/CD8 double-positive (DP) cells and the CD44-CD25+ subset of the CD4/CD8 double-negative (DN) cells. Of note, these populations also express HK-1, raising the possibility of autocrine or paracrine pathways influencing T-cell development as we previously reported for B-cell development. Consistent with this, the detrimental effect of tachykinin antagonists could be partially overcome with exogenous HK-1 peptide.
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PMID:T-cell developmental blockage by tachykinin antagonists and the role of hemokinin 1 in T lymphopoiesis. 1279 65

Herein we provide evidence that substance P (SP) and its neurokinin-1 receptor (NK-1R) expressed on thymocytes counteract thymus depletion induced by neonatal capsaicin (CPS) treatment by affecting thymocyte proliferation and apoptotic death. SP administration reversed the CPS-mediated inhibitory effects on the total thymocyte number and subset distribution, namely CD4+ and CD4- CD8- cells, through its interaction with NK-1R as shown by concomitant NK-1R (SR140333) antagonist administration. SP-induced enhancement of thymus cellularity parallels its ability of inhibiting the thymocyte apoptotic program. Indeed, exogenously administered SP completely nullified CPS-induced apoptosis, and SR140333 abrogated the SP-mediated protective effect. SP administration also stimulated concanavalin A (Con A)-induced thymocyte proliferation of CPS-treated rats, completely reversing the CPS-induced inhibition. The SP-mediated stimulation of Con A-induced thymocyte proliferation was NK-1R dependent as shown by concomitant administration of SP and SR140333 to CPS-treated rats. Our results also demonstrate that CPS treatment induces a marked decrease of thymocyte PPT-A mRNA level and endogenous SP content as evaluated by quantitative RT-PCR, in situ hybridization and cytofluorimetric analysis. By contrast, NK-1R mRNA levels were increased in thymocytes from CPS-treated rats. Exogenous SP administration augmented PPT-A, SP and NK-1R thymocyte expression in CPS-treated rats, and this enhancement was antagonized by SR140333 administration. Overall, our results strongly suggest that the immunomodulatory effects of neonatal CPS treatment on rat thymocyte functions are dependent on vanilloid-mediated regulation of SP and NK-1R functional expression by neuronal and immune cells.
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PMID:Neonatal capsaicin treatment affects rat thymocyte proliferation and cell death by modulating substance P and neurokinin-1 receptor expression. 1506 7

Psoriasis, a TH1-induced disorder, is not more common in human immunodeficiency virus (HIV) infection than in the general population. However, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. The paradoxical exacerbation of psoriasis in AIDS has not been fully explained. Various explanations have been proposed including (a) the reduction of Langerhans' cells (LCs) in HIV disease, (b) the direct epidermal proliferative effect of HIV, (c) the altered cytokine profile in HIV disease, (d) HIV-induced macrophage nitric oxide (NO) production, (e) the increased CD8/CD4 T-cell ratio in HIV infection and (f) the increased colonization of skin by Staphylococcus aureus. However, the observations that (a) LCs cells play an important role in the pathogenesis of psoriasis and a variety of topical and systemic psoriasis treatments cause a reversible decrease in LC function, (b) psoriasis may improve in end-stage HIV infection, (c) overproduction of some TH2 cytokines and underproduction of IL-2 in HIV infection, and (d) the presence of NO favors a TH2 response over a TH1 response make the first four explanations difficult to interpret. Since psoriasis is exacerbated in HIV infection possibly due to the increased staphylococcal colonization, and psoriatic keratinocytes could aggravate HIV infection through production of TNF-alpha, it could be reasoned that in HIV-positive psoriatics a strong vicious cycle is present between the degree of immune deficiency and the staphylococcal colonization, explaining the poor prognosis of both AIDS and psoriasis in these patients. With reference to the studies which indicate significant involvement of substance P (SP) in the pathogenesis of psoriasis and on the other hand increased release of this agent by HIV-infected immune cells it is proposed that SP plays an important role in creating the paradox. Since in HIV-positive psoriatics the source of SP is largely immune cells not neurons, capsaicin, which exerts its action selectively on a subpopulation of neurons, could not be of significant therapeutic value. As SP significantly enhances HIV-1 replication in latently infected immune cells, psoriatic lesions, being heavily infiltrated with immune cells and having high concentrations of SP, could serve as high HIV-replication foci, with the resultant rapid progression of the infection towards AIDS. Additionally, given that lipopolysaccharide is supposed to exacerbate psoriasis, increase of gram-negative infections or cutaneous colonization with these organisms in AIDS may partly explain the paradox. Understanding the HIV-induced immunodysregulation that is associated with psoriasis in some HIV-seropositive patients may assist in the delineation of the immunopathogenesis of the disease in HIV-seronegative psoriatics.
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PMID:Paradoxical exacerbation of psoriasis in AIDS: proposed explanations including the potential roles of substance P and gram-negative bacteria. 1511 14

The effort to explore the specific autoimmune mechanisms of urinary bladder has long been hindered due to a lack of proper animal models. To better elucidate this issue, we developed a novel line of transgenic (Tg) mice, designated as URO-OVA mice, that express the model Ag OVA as a "self"-Ag on the bladder epithelium. URO-OVA mice are naturally tolerant to OVA and show no response to OVA stimulation. Adoptive transfer of naive OVA-specific T cells showed cell proliferation, activation, and infiltration but no bladder histopathology. In contrast, adoptive transfer of activated OVA-specific T cells induced OVA-mediated histological bladder inflammation. Increased mast cells and up-regulated mRNA expressions of TNF-alpha, nerve growth factor, and substance P precursor were also observed in the inflamed bladder. To further facilitate bladder autoimmunity study, we crossbred URO-OVA mice with OVA-specific CD8(+) TCR Tg mice (OT-I mice) to generate a dual Tg line URO-OVA/OT-I mice. The latter mice naturally acquire clonal deletion for autoreactive OT-I CD8(+) T cells (partial deletion in the thymus and severe deletion in the periphery). Despite this clonal deletion, URO-OVA/OT-I mice spontaneously develop autoimmune cystitis at 10 wk of age. Further studies demonstrated that the inflamed bladder contained infiltrating OT-I CD8(+) T cells that had escaped clonal deletion and gained effector functions before developing histological bladder inflammation. Taken together, we demonstrate for the first time that the bladder epithelium actively presents self-Ag to the immune system and induces CD8(+) T cell tolerance, activation, and autoimmune response.
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PMID:Urinary bladder epithelium antigen induces CD8+ T cell tolerance, activation, and autoimmune response. 1718 94

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