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)

Lipopolysaccharide (LPS) is implicated in many respiratory tract inflammatory diseases. Tachykinins, especially substance P (SP) through the NK-1 receptor, mediate leukocyte adhesion to the endothelial or airway epithelial cells. Here we assessed the enhancement by LPS of tachykinin-mediated neutrophil adherence to alveolar epithelial cells, and associated interleukin-1 beta (IL-1beta) and tumor necrosis factor (TNF-alpha) release. Neutrophil adherence to A549 epithelial cell was not increased by LPS (100 ng/ml), or SP (10(-)(12)-10(-)(8) M) alone, but was significantly enhanced by their combination (LPS + SP). Neutrophil adherence to epithelial cells induced IL-1beta and TNF-alpha release from A549 cells either spontaneously or stimulated by SP or LPS. LPS + SP significantly enhanced IL-1beta and TNF-alpha release. The NK-1 receptor antagonist L-732,138 inhibited this enhancement response. Prevention of neutrophil adherence by CD11b/CD18 blocking antibody or by placing a filter on the epithelial monolayer diminished spontaneous or LPS + SP-enhanced IL-1beta and TNF-alpha release. Pretreatment with the serine protease inhibitor cocktail also inhibited LPS + SP-enhanced neutrophil adherence-dependent IL-1beta and TNF-alpha release as well as their mRNA expression. In conclusion, we have demonstrated LPS enhanced SP-mediated neutrophil adherence and associated IL-1beta and TNF-alpha release from the A549 epithelial monolayer, partly through NK-1 receptors. Neutrophil adherence to epithelial cells may release serine protease to induce IL-1beta and TNF-alpha release and their synthesis.
 ...
PMID:Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release. 1106 31

The lung is richly supplied with peptidergic nerves that store and secrete substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides known to potently modulate leukocyte function in vitro and airway inflammation in vivo. We examined the effect of SP, VIP and the novel sensory neuropeptide secretoneurin (SN), as well as of interleukin (IL)-8, IL-6, IL-1 beta, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF), all associated with acute lung injury, on human neutrophil migration across a 5-mu pore polycarbonate filter system covered by human lung fibroblast monolayers. Additionally, we tested the ability of these neuropeptides to elicit neutrophil adhesion to fibroblast monolayers. SP, but not VIP and SN, may be important in directly influencing neutrophil adhesion to and subsequent migration across a subendothelial barrier of fibroblasts and extracellular matrix towards lung inflammatory sites. The effect was mainly mediated by neurokinin (NK)-1 receptors, as evaluated by a specific NK-1 antagonist, [[(S,S)Pro-Leu(spiro-y-lactam)]9,10, Trp11]substance P (1-11), whereas a specific NK-2 receptor antagonist, [Tyr5, D-Trp6,8,9, Lys10]neurokinin A (4-10), was ineffective. The SP analog septide and the NK-1 receptor agonist ([Sar9 Met(O2)11)SP were comparably effective. Furthermore, the SP effect was concentration and time dependent. However, the other tested neuropeptides might also affect neutrophil recruitment in inflammatory lung by modulating other lung cell functions. Additionally, all tested cytokines stimulated neutrophil transfibroblast migration in vitro, except IL-6. In conclusion, SP in concert with proinflammatory cytokines may regulate neutrophil interstitial accumulation and their traffic to the alveolar space in lung inflammation.
 ...
PMID:Influence of neuropeptides on neutrophil adhesion and transmigration through a lung fibroblast barrier in vitro. 1120 62

Substance P (SP) can stimulate secretion of tumor necrosis factor-alpha (TNF-alpha) from astrocytes stimulated with lipopolysaccharide (LPS). In this study, we have examined whether an aqueous extract of Chilbokeum inhibits secretion of TNF-alpha from primary cultures of rat astrocytes. Chilbokeum (10 microg/ml) significantly inhibited the TNF-alpha secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by Chilbokeum. Treatment of Chilbokeum (10 and 100 microg/ml) to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. Moreover, the secretion of TNF-alpha by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Our results suggest that Chilbokeum may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that Chilbokeum has an antiinflammatory activity in the central nervous system.
 ...
PMID:Inhibitory effect of tumor necrosis factor-alpha secretion from rat astrocytes by Chilbokeum. 1132 53

Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), respectively. We previously demonstrated that NK1 and NK2 receptors are present on human monocytes, SP and NKA inducing superoxide anion production and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. NK2 receptor stimulation also triggered an enhanced respiratory burst in monocytes isolated from rheumatoid arthritis (RA) patients. This study was aimed to evaluate the in vitro and ex-vivo effects of cyclosporin A (CsA) on tachykinins-evoked TNF-alpha release from monocytes of healthy donors and RA patients. CsA (100 ng/ml) potently inhibited phorbol ester- and tachykinin-evoked TNF-alpha secretion. In RA patients treated with CsA (Sandimmun Neoral 2.5 mg/kg/day, a significant time-dependent reduction in TNF-alpha secretion from monocytes was measured. This may contribute to the CsA therapeutic activity in RA.
 ...
PMID:Tachykinin activation of human monocytes from patients with rheumatoid arthritis: in vitro and ex-vivo effects of cyclosporin A. 1138 4

Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)-beta and tumor necrosis factor-alpha in BM stroma. TGF-beta production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.
 ...
PMID:Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study. 1167 40

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.
 ...
PMID:Substance P enhances HIV-1 replication in latently infected human immune cells. 1173 Sep 41

Stimulation of sensory nerves can lead to release of peptides such as substance P (SP) and consequently to neurogenic inflammation. We studied the role of bacterial lipopolysaccharide (LPS) in regulating SP-induced inflammation. Experimental cystitis was induced in female mice by intravesical instillation of SP, LPS, or fluorescein-labeled LPS. Uptake of fluorescein-labeled LPS was determined by confocal analysis, and bladder inflammation was determined by morphological analysis. SP was infused into the bladders of some mice 24 h after exposure to LPS. In vitro studies determined the capacity of LPS and SP to induce histamine and cytokine release by the bladder. LPS was taken up by urothelial cells and distributed systemically. Twenty-four hours after instillation of LPS or SP, bladder inflammation was characterized by edema and leukocytic infiltration of the bladder wall. LPS pretreatment enhanced neutrophil infiltration induced by SP, increased in vitro release of histamine, tumor necrosis factor-alpha, and interferon-gamma, and significantly reduced transforming growth factor-beta1 release. These findings suggest that LPS amplifies neurogenic inflammation, thereby playing a role in the pathogenesis of neurogenic cystitis.
 ...
PMID:LPS-sensory peptide communication in experimental cystitis. 1178 33

Yuldahansotang (YH-Tang), a Sasang Constitutional prescription composed of seven herbal mixtures, has been developed as a formula to prevent and treat cerebral infarction (CI) of Taeumins. However, the mechanisms by which this formula affects CI remain unknown. Previously, regulation of serum cytokine levels by YH-Tang has been observed in individuals at the acute stage of CI disease. It is uncertain whether this is a cause or a result of the disease process. In this study, we investigated whether YH-Tang inhibited secretion of inflammatory cytokines from human astrocytes. YH-Tang regulated the cytokine secretions in astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). YH-Tang significantly inhibited interleukin (IL)-1, IL-4, IL-6 and tumor necrosis factor-alpha (TNF-alpha) secretion in astrocytes stimulated with SP and LPS, but did not inhibit interferon-y (IFN-gamma) and IL-2 secretion significantly. IL-1 has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Therefore, we investigated whether IL-1 mediated inhibition of TNF-alpha secretion from astrocytes by YH-Tang. Incubation of human astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS and SP. These results suggest that YH-Tang may indirectly inhibit TNF-alpha secretion by inhibiting IL-1 secretion. Moreover, these findings indicate that YH-Tang has regulatory effects on cytokine secretion in an acute CI patient.
 ...
PMID:Cytokine production regulation in human astrocytes by a herbal combination (Yuldahansotang). 1202 45

Previously, we have shown that primary afferent sensory neurons are necessary for disease activity in T cell-mediated immune hepatitis in mice. In the present study, we analyzed the possible role of substance P (SP), an important proinflammatory neuropeptide of these nerve fibers, in an in vivo mouse model of liver inflammation. Liver injury was induced by bacterial lipopolysaccharide (LPS) in D-galactosamine (GalN)-sensitized mice. Depletion of primary afferent nerve fibers by neonatal capsaicin treatment down-regulated circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) and protected mice from GalN/LPS-induced liver injury. Likewise, pretreatment of mice with antagonists of the SP-specific neurokinin-1 receptor (NK-1R), i.e., (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-azabicyclo(2.2.2.)-octan-3-amine (CP-96,345) and (2S,3S)3-([3,5-bis(trifluoromethyl)phenyl]methoxy)-2-phenylpiperidine (L-733,060), dose dependently protected mice from GalN/LPS-induced liver injury. The presence of the NK-1R in the murine liver was demonstrated by reverse transcription-polymerase chain reaction, sequence analysis, and immunocytochemistry. NK-1R blockade reduced inflammatory liver damage, i.e., edema formation, neutrophil infiltration, hepatocyte apoptosis, and necrosis. To get further insight into the mechanism by which receptor blockade attenuated GalN/LPS-induced liver damage, we analyzed plasma levels and intrahepatic expression of TNFalpha, IFNgamma, interleukin (IL)-6, and IL-10. NK-1R blockade clearly inhibited GalN/LPS-induced production of TNFalpha and IFNgamma, whereas synthesis of the hepatoprotective cytokines IL-6 and IL-10 was increased. NK-1 receptor antagonists might be potent drugs for treatment of inflammatory liver disease, most likely by inhibiting SP effects.
 ...
PMID:Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury. 1264 50

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.
 ...
PMID:Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis. 1460 51


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