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)

Sunburned skin is characterized by expanded numbers of macrophages (ultraviolet [UV]-MPH), and these UV-MPH differ from Langerhans cells (LC) in their abilities to initiate T-cell-mediated immune reactions. UV-MPH and LC may themselves be differentially responsive to the surrounding milieu, which may in turn modulate their immunoregulatory activity. We asked whether immunologic signal responsiveness, as assessed by cytosolic calcium mobilization, differed among normal human LC, UV-MPH, and normal blood monocytes. LC from normal skin and UV-MPH from UV-exposed skin were distinguished from keratinocytes in epidermal cell suspensions by labeling with anti-HLA-DR. Intracellular calcium content was monitored in real time with the calcium indicator, indo-1, after cross-linking Fc gamma RI, Fc gamma RII, CD11b, CD11c, or CD18 molecules, or addition of interleukin-1 alpha, IL-1 beta, interferon-gamma, bradykinin, substance P, or FMLP. Using flow cytometric analysis of cell suspensions, UV-MPH and blood monocytes were triggered by cross-linking Fc gamma RII (flux of 6.05 and 12.2, respectively). UV-MPH could also be triggered by Fc gamma RI crosslinking and FMLP (flux of 6.41 and 15.54, respectively). By contrast, none of these inflammatory stimuli could cause cytosolic calcium mobilization in normal LC (Flux of -0.2 by FcRII, and 0.18 by FMLP). Because LC calcium flux may be dependent upon extracellular attachments, LC were anchored onto fibronectin-coated coverslips and then their Fc gamma RII was crosslinked in a continuous flow chamber. However, image analysis also failed to detect calcium flux. Neither population responded to interleukin-1, interferon-gamma, bradykinin, substance P, or beta 2 integrin crosslinking. These results indicate that blood monocytes and infiltrating macrophages differ substantially from LC in their responses to immune complexes and chemoattractants. Differential responsiveness to the inflammatory milieu may influence the antigen presenting or effector capabilities of these populations.
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PMID:Differential extracellular signaling via Fc gamma R and FMLP in functionally distinct antigen-presenting cell subsets: ultraviolet-induced epidermal macrophages versus Langerhans cells. 766 17

Interleukin-1 (IL-1) induces substance P (SP) gene expression in cultured rat superior cervical ganglion (SCG) explants. In order to study the molecular mechanism of this action of IL-1, the presence of an interleukin-1 receptor (IL-1R) activity and the identity of an mRNA homologous to known IL-1R sequence was determined in SCG. The SP increase is blocked by recombinant IL-1 receptor antagonist protein, so IL-1 must be interacting with a specific receptor. We have cloned cDNA homologous to IL-1R type I from rat SCG using a reverse transcription-polymerase chain reaction (RT-PCR). The resulting cDNA sequence is strongly homologous with mouse and human IL-1R cDNA of the T cell and fibroblast type (type I; encoding an 80-kDa protein). mRNA specific for IL-1R can be readily detected in intact SCG by quantitative RT-PCR and S1 hybridization. However, the level of IL-1R mRNA increases 3-6-fold by 2 days in culture. This increase is independent of the presence of dexamethasone, IL-1 beta or IL-1 receptor antagonist protein ligands. The increase of IL-1R following explantation, a model of nerve injury, may provide a mechanism linking inflammatory signalling to neuronal phenotypic changes.
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PMID:An mRNA homologous to interleukin-1 receptor type I is expressed in cultured rat sympathetic ganglia. 768 99

It has become increasingly clear that immune cytokines perform growth and differentiation functions in the nervous system similar to those performed in the immune system. In previous studies we have shown that interleukin-1 beta (IL-1 beta) raises substance P (SP) and the mRNA coding for its preprotachykinin precursor in cultured sympathetic superior cervical ganglia (SCG) (Jonakait and Schotland, 1990; Hart et al., 1991a). The action of IL-1 is blocked both by depolarization of the ganglia and by glucocorticoid hormones (Hart et al., 1991a). In the present report, we have found that IL-1 does not act directly upon neurons to raise SP, but rather induces the production of a soluble intermediate molecule that raises both SP and the cholinergic-specific enzyme ChAT. Its induction by IL-1 is blocked by the synthetic glucocorticoid hormone dexamethasone; its action is compromised under depolarizing conditions. Because medium conditioned by IL-1 (IL-1CM) is functionally similar to leukemia inhibitory factor (LIF), we sought to determine whether this molecule might be an active constituent of IL-1CM. Immunoprecipitation with an antiserum directed against LIF eliminated large proportions of SP-inducing activity from IL-1CM. In addition, steady-state levels of mRNA coding for LIF are increased by IL-1 treatment of SCG. These data suggest that LIF, induced by IL-1, may ultimately be responsible for the IL-1 induction of SP.
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PMID:Interleukin-1 induces substance P in sympathetic ganglia through the induction of leukemia inhibitory factor (LIF). 768 75

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

We studied interleukin-1 beta (IL-1 beta), beta 2-microglobulin (beta 2-m), beta-endorphin, substance P, neuropeptide Y and somatostatin concentrations in the cerebrospinal fluid of 13 patients with dementia of the Alzheimer type (DAT), 13 patients with multi-infarct dementia (MID) and 15 age-matched control subjects. Substance P was significantly lower in DAT than in controls (P < 0.05), as well as somatostatin in DAT as compared to both controls (P < 0.01) and MID (P < 0.05), whereas beta 2-m was higher in DAT than in controls (P < 0.01). Neuropeptide Y, beta-endorphin and IL-1 beta showed similar concentrations in the three groups studied. A significantly positive correlation was observed between IL-1 beta and substance P (r = 0.79, P < 0.01) and somatostatin (r = 0.75, P < 0.05) in DAT, which was not observed in MID. In addition, beta 2-m showed a negative correlation with IL-1 beta (r = -0.73, P < 0.05) in DAT, and age correlated negatively with IL-1 beta in controls and MID, but positively in DAT. Therefore, these results support the idea that an altered relationship may exist in Alzheimer's disease between the nervous and immune system.
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PMID:Relationship of interleukin-1 beta and beta 2-microglobulin with neuropeptides in cerebrospinal fluid of patients with dementia of the Alzheimer type. 769 56

Several hypothalamic neuropeptides and amino acids are known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not known. In this study, we have evaluated the interaction between neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.c.v.) cannula and 9-12 days later an intrajugular cannula for frequent blood sampling. The next day, rats received i.c.v. either saline (SAL, 3 microliters, controls) or a neuropeptide: the opioid beta-endorphin (beta-END; 2.9 nmol), the tachykinin neuropeptide K (NPK, 2.5 nmol) or the cytokine interleukin-1 beta (IL-1 beta, 5.9 pmol) in SAL. The LH response to 2 consecutive i.v. injections of NMDA (5 mg/kg) at 30 min intervals was evaluated. In control rats, each NMDA injection evoked a significant release of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an inhibitory effect, enhanced the LH response to NMDA. The peak plasma LH levels after each NMDA injection and the cumulative LH responses were significantly higher in peptide-treated than in control rats. This peculiar ability of the peptides that inhibit LH release in castrated rats, to potentiate the NMDA-induced LH release in the presence of gonadal steroids was further validated in female rats treated with an opiate receptor agonist, morphine (MOR) which is also known to suppress LH release in ovariectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The hypothalamic peptides, beta-endorphin, neuropeptide K and interleukin-1 beta, and the opiate morphine, enhance the excitatory amino acid-induced LH release under the influence of gonadal steroids. 782 26

Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine that appears to be an integral component of the bidirectional signalling between the immune and central nervous systems. It is produced in the hypothalamus and has been shown to inhibit the hypothalamo-pituitary-gonadal axis and to activate the hypothalamo-pituitary-adrenal axis. IL-1 beta is reported to up-regulate the tachykinin, substance P (SP), in the peripheral nervous system. We have recently observed that members of the hypothalamic tachykinin family including SP, neurokinin A (NKA) and two N-terminal extended forms of NKA (neuropeptides kappa and gamma), inhibit hypothalamic LHRH and pituitary LH release and stimulate adrenal corticosterone secretion. The similarity in the endocrine effects of the tachykinins and the cytokine prompted us to test the hypothesis that IL-1 beta may stimulate the hypothalamic tachykinins, which would then mediate the neuroendocrine effects of IL-1 beta. First, the effects of IL-1 beta on the in vitro release of NKA-like immunoreactivity (NKA-li) from the hypothalamus was examined. Addition of 10 nM IL-1 beta significantly increased NKA-li release from the hypothalami of castrated rats, but not from the hypothalami of intact rats. To identify the site of IL-1 beta action, the effects of intraventricular IL-1 beta (100 ng) on NKA-li levels in various hypothalamic sites of intact and castrated rats were examined. The results showed that IL-1 beta increased NKA-li selectively in the median eminence (ME) and arcuate nucleus (ARC) of castrated rats only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of interleukin 1 beta on the hypothalamic tachykinin, neurokinin A. 785 71

Lipopolysaccharide (LPS) caused a concentration-dependent increase of released and cell-associated interleukin-1 (IL-1) in resident peritoneal macrophages from the mouse. LPS was about 30 times more potent at stimulating the level of cell-associated IL-1 than it was at stimulating the release of IL-1. Human recombinant tumour necrosis factor-alpha (TNF-alpha) and the calcium ionophores A23187 and ionomycin induced a concentration-dependent increase of cell-associated IL-1 but failed to cause release of IL-1 at concentrations producing maximal stimulation of cell-associated IL-1. The phorbol ester, 4 beta-phorbol dibutyrate, stimulated the release of IL-1 from mouse macrophages but failed to induce an increase in cell-associated IL-1. Substance P, neurokinin A, neurokinin B, calcitonin gene-related peptide and platelet-activating factor did not increase the released or cell-associated IL-1 in mouse macrophages. These agents also failed to alter released or cell-associated IL-1 stimulated by LPS, 1 microgram ml-1. It appears that a calcium signal is sufficient for the transcription and translation of IL-1 mRNA but does not result in the secretion of biologically active forms of IL-1. Our data also indicate that different intracellular signals may control the release and the cell accumulation of IL-1. We conclude that inflammatory mediators may independently increase either the release of, or the cell accumulation of IL-1.
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PMID:Stimulation and release of interleukin-1 from peritoneal macrophages of the mouse. 787 2

A large body of recent evidence suggests that a number of inhibitory and excitatory neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytokine [interleukin-1 beta (IL-1 beta)], or tachykinin [neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeks postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg) at 30-min intervals. Blood samples for LH measurements were withdrawn immediately before and 10 min after each NMDA injection. The results show that intracerebroventricular beta END, IL-1 beta, or NPK inhibited LH release. Multiple injections of NMDA did not alter the existing pattern of LH secretion in castrated control rats. However, similar NMDA injections completely prevented the decrease in LH release by beta END, IL-1 beta, or NPK. Plasma LH levels in these rats remained within the range seen in untreated control rats throughout the 120-min duration of the experiment, and NMDA injections at 30-min intervals evoked pulses of LH that resembled those seen normally in castrated rats. The blockade of the inhibitory effects of the three peptides by NMDA and previous knowledge of hypothalamic sites of NMDA action suggest that EAA systems may represent a common pathway down-stream in the hypothalamic LHRH-regulating circuitry to mediate diminution of LH release by inhibitory peptides. Further, their inhibitory influence may be exerted either directly at the level of LHRH neurons and/or by diminution in EAA efflux, leading to suppression of LHRH and LH release.
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PMID:Evidence that luteinizing hormone suppression in response to inhibitory neuropeptides, beta-endorphin, interleukin-1 beta, and neuropeptide-K, may involve excitatory amino acids. 831 64

The present study establishes that tumor necrosis factor-alpha (TNF-alpha) induction of sympathetic substance P (SP) requires sequential induction of both interleukin (IL-1) and leukemia inhibitory factor (LIF). TNF-alpha dose-dependently induces SP, an induction that is secondary to an increase in the SP precursor, preprotachykinin (PPT), mRNA. Since TNF-alpha conditioned medium (CM) mimics the effect of TNF-alpha by raising SP, actions that are not antagonized by a neutralizing TNF-alpha antibody, TNF-alpha induction of SP is mediated by a soluble intermediate or intermediates. The blockade of TNF-alpha action by a specific IL-1 receptor antagonist and the induction of IL-1 mRNA by TNF-alpha suggest that IL-1 is one of the intermediates. Moreover, because immunoprecipitation with LIF antibodies decreases SP-inducing activity of TNF-alpha CM, and because LIF mRNA is also induced by TNF-alpha, LIF is a second intermediate. Furthermore, TNF-alpha-induced LIF mRNA is blocked by the IL-1 receptor antagonist, whereas IL-1-induced LIF mRNA is not affected by TNF-alpha antibodies, suggesting that TNF-alpha first induces IL-1, and IL-1 subsequently induces LIF. These data suggest that TNF-alpha induces SP in sympathetic ganglia through the sequential inductions of IL-1 and LIF.
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PMID:Tumor necrosis factor-alpha induces substance P in sympathetic ganglia through sequential induction of interleukin-1 and leukemia inhibitory factor. 859 5


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