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)

The neuropeptide substance P (SP) is known to increase cell-mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP, may represent a model for the analysis of immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10(-10)-10(-6) M) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by 3H-thymidine incorporation in peripheral blood lymphocytes from 34 HIV-infected patients (16 asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/PGL HIV-infected patients, SP 10(-7) M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A, in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide-dependent immunoregulatory systems in HIV infection.
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PMID:Disturbed immunoregulatory properties of the neuropeptide substance P on lymphocyte proliferation in HIV infection. 751 68

Substance P (SP), a member of the tachykinin family of neuropeptides, is an important immunomodulator of lymphocyte and monocyte/macrophage function. We have examined the effects of SP on human immunodeficiency virus type 1 (HIV-1) infection of peripheral blood monocyte-derived macrophages (MDMs) in vitro. Human monocytes isolated by Ficoll gradient followed by adherence were maintained in vitro for 10 days and infected with HIV-1. The addition of SP resulted in a 2- to 8-fold-enhanced HIV-1 expression in the MDMs isolated from 7 of 13 healthy donors as determined by reverse transcriptase (RT) activity and p24 protein expression assays, as compared to control cultures incubated with HIV-1 alone. There was no correlation observed, however, between SP-stimulated TNF production and HIV-1 expression in MDMs obtained from a subset of these donors. These effects of SP on HIV-1 expression in MDMs in vitro may have in vivo implications relevant to modulation of monocyte/macrophage functions, to HIV-1 infection of monocytes/macrophages, and to the immunopathogenesis of HIV-1 infection.
AIDS Res Hum Retroviruses 1996 Feb 10
PMID:Substance P modulates human immunodeficiency virus replication in human peripheral blood monocyte-derived macrophages. 883 96

Interleukin-6 (IL-6) is a proinflammatory cytokine whose synthesis is induced by a variety of stimuli including interleukin-1 (IL-1), substance P (SP), and histamine. Because IL-6 has been implicated in the etiopathology of different human diseases including multiple myeloma, rheumatoid arthritis, multiple sclerosis, acquired immunodeficiency syndrome dementia complex, and Alzheimer's disease, its inhibition may be of therapeutic interest. A main demand on an effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis independently of the inducing stimulus. We therefore used human astrocytoma cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1beta, SP, and histamine. Whereas the antioxidant pyrrolidinedithiocarbamate was only able to inhibit IL-1beta-induced IL-6 expression, inhibition of protein kinase C prevented IL-6 expression induced by all three substances. Promoter deletion analysis revealed that IL-1beta-induced IL-6 expression required the transcription factor nuclear factor-kappaB (NF-kappaB), whereas SP- and histamine-induced IL-6 synthesis was essentially controlled by NF-IL-6. These findings suggest that inhibition of protein kinase C or a combinatory inhibition of NF-IL-6 and NF-kappaB binding are strategies to effectively suppress IL-6 synthesis. They therefore provide the basis for the development of antiinflammatory drugs used to treat disorders in which IL-6 is pathogenically involved.
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PMID:Substance P and histamine induce interleukin-6 expression in human astrocytoma cells by a mechanism involving protein kinase C and nuclear factor-IL-6. 952 75

In vitro and in vivo studies have indicated that there is an important relationship between morphine and neuropeptide substance P (SP). We therefore investigated the interaction of morphine and cultured human immune cells on the expression of SP, a neuropeptide which we have recently demonstrated to be produced by human monocytes and lymphocytes. Morphine up-regulated SP production in human mononuclear phagocytes and lymphocytes at both the mRNA and the protein level. In addition, morphine induced SP receptor (NK-1R) expression in human lymphocytes. The specific morphine receptor antagonist (naltrexone) blocked morphine-induced SP expression in human mononuclear phagocytes, supporting the concept of authentic morphine receptor-mediated regulation. Since SP modulates neurogenic inflammation and immunologic events, these data suggest that morphine-induced SP expression in cells of the immune system may be of importance in the pathogenesis of immune-mediated diseases, including neuroimmunologic diseases and AIDS.
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PMID:Morphine Up-regulates expression of substance P and its receptor in human blood mononuclear phagocytes and lymphocytes. 1110 84

The neuropeptide, substance P, is a potent modulator of neuroimmunoregulation. Substance P and its receptor modulate HIV infection. HIV-seropositive men had significantly higher plasma substance P levels compared with uninfected controls, which were associated with decreased CD16 and CD56 natural killer (NK) cell populations. The changes in plasma substance P levels and decreases in NK subsets did not correlate with CD4 cell levels, but a diurnal pattern was suggested for substance P. The balance between substance P expression and functions of immune cells may be important in the immunopathogenesis of HIV infection.
AIDS 2001 Oct 19
PMID:Elevated substance P levels in HIV-infected men. 1160 Aug 35

Substance P (SP) is a potent modulator of neuroimmunoregulation. SP receptors are present on human monocytes and T lymphocytes, and SP alters the function of these immune cells. We investigated the effects of SP on HIV-1 replication in latently infected human immune cells. SP significantly enhanced HIV-1 replication in the latently infected promonocytic cell line (U1) and T lymphocyte line (ACH-2) stimulated with tumor necrosis factor (TNF-alpha). When added to these cells in combination with TNF-alpha, SP also enhanced HIV-1 gag gene expression in U1 and ACH-2 cells. This stimulatory effect of SP was associated with the activation of HIV-LTR (long terminal repeat) driven chloramphenicol acetyltransferase (CAT) gene expression, and could be blocked by pretreatment of U1 and ACH-2 cells with an SP receptor antagonist RP-67,580, indicating specific SP receptor-mediated regulation. Furthermore, the addition of SP to the cultures of latently infected peripheral blood mononuclear cells isolated from HIV-1-infected patients enhanced HIV-1 gag gene expression. Thus, SP may play a potentially important role as a positive regulator of HIV-1 replication in latently infected monocytes and lymphocytes. These observations may have significant implications toward understanding the role of neuropeptide SP in the immunopathogenesis of HIV-1 infection and AIDS.
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PMID:Substance P enhances HIV-1 replication in latently infected human immune cells. 1173 Sep 41

Substance P (SP), a potent modulator of neuroimmunoregulation, is expressed in human immune cells. We observed elevated plasma SP levels in HIV-infected men compared with uninfected subjects. In the present study, we investigated the possible cellular source of the increased SP level caused by HIV infection. Using real-time reverse transcriptase-polymerase chain reaction, we demonstrated that monocyte-derived macrophages (MDM) and lymphocytes from both placental cord blood and adult peripheral blood expressed SP mRNA, which was significantly increased by HIV infection. HIV-induced SP expression was positively related to virus replication in the infected MDM. Purified recombinant HIV envelope glycoprotein 120 (gp120) derived from both the macrophage-tropic strain (MN) and the T lymphocyte-tropic strain (IIIB), when added to MDM cultures, enhanced SP mRNA expression. The gp120-induced SP expression was abrogated by pretreating the cells with soluble CD4. Furthermore, the activation of HIV in the latently infected promonocytic cell line (U1) and T-cell line (ACH-2) up-regulated SP mRNA expression. These data support the hypothesis that interaction of HIV and SP may have significant in vivo relevance to the immunopathogenesis of HIV infection and AIDS.
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PMID:HIV enhances substance P expression in human immune cells. 1191 72

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.
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PMID:Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology. 1276 96

Cryptosporidiosis, caused by Cryptosporidium parvum, is self-limited in immunocompetent hosts but may cause chronic diarrhea in patients with acquired immunodeficiency syndrome (AIDS). Substance P (SP), a neuropeptide belonging to the tachykinin family, is expressed in gastrointestinal tract and can cause electrogenic chloride anion secretion. Therefore, we studied SP mRNA and protein expression in jejunal tissue samples of patients with AIDS with naturally occurring chronic cryptosporidiosis and healthy volunteers with mild cryptosporidiosis or asymptomatic infection after experimental C. parvum challenge. SP mRNA was associated with symptoms in cryptosporidiosis. SP protein levels were greater in symptomatic than asymptomatic volunteers. Similarly, greater expression of SP mRNA and protein were noted in patients with AIDS with chronic cryptosporidiosis versus immunocompetent volunteers with self-limited infection. This study demonstrates a direct correlation between SP levels and disease severity and may imply that SP plays a role in diarrhea mediation.
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PMID:Substance P expression correlates with severity of diarrhea in cryptosporidiosis. 1285 86

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


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