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 and the cytokine transforming growth factor-beta are potent chemotactic factors for monocytes or polymorphonuclear cells. They are present in synovial fluid of arthritic patients, and participate in the pathogenesis of arthritis. We investigated, in vitro, the effect of two non-steroidal anti-inflammatory drugs, ibuprofen and diclofenac, on the chemotactic effect of substance P and transforming growth factor-beta at concentrations that can be present in the synovial fluid of arthritic patients. Both drugs decrease the chemotaxis induced by substance P and transforming growth factor-beta, at concentrations that can be easily reached in the synovial fluid during therapy. This event could be involved in the effect of some non-steroidal anti-inflammatory drugs on the development and progress of arthritic disease.
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PMID:Effect of ibuprofen and diclofenac on the chemotaxis induced by substance P and transforming growth factor-beta on human monocytes and polymorphonuclear cells. 750 66

The effects of vasoactive intestinal peptide (VIP) on human IgA1 and IgA2 production were studied. In unfractionated small resting B cells stimulated with anti-CD40 monoclonal antibody (mAb), VIP induced IgA1 and IgA2 production without affecting the production of IgG1, IgG2, IgG3, IgG4, IgM, or IgE. When small B cells were separated into sIgA1+, sIgA2+, sIgA1- and sIgA2- B cells, anti-CD40 mAb plus VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2- B cells, respectively, while having no effect on sIgA1+ and sIgA2+ B cells. This induction by VIP was specific, since anti-CD40 mAb plus other neuropeptides, i.e., somatostatin or substance P, had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Further, anti-CD40 mAb plus various cytokines, including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor-beta, low molecular weight B cell growth factor, and interferon-gamma, did not induce IgA1 and IgA2 production by sIgA1- and sIgA2- B cells, respectively. These results indicate that in the presence of anti-CD40 mAb, VIP induces IgA1 and IgA2 production by isotype switching.
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PMID:Vasoactive intestinal peptide specifically induces human IgA1 and IgA2 production. 752 70

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic polypeptide, distantly related to transforming growth factor-beta (TGF-beta), originally isolated by virtue of its ability to induce dopamine uptake and cell survival in cultures of embryonic ventral midbrain dopaminergic neurons, and more recently shown to be a potent neurotrophic factor for motorneurons. The biological activities and distribution of this molecule outside the central nervous system are presently unknown. We report here on the mRNA expression, biological activities and initial receptor binding characterization of GDNF and a shorter spliced variant termed GDNF beta in different organs and peripheral neurons of the developing rat. Both GDNF mRNA forms were found to be most highly expressed in developing skin, whisker pad, kidney, stomach and testis. Lower expression was also detected in developing skeletal muscle, ovary, lung, and adrenal gland. Developing spinal cord, superior cervical ganglion (SCG) and dorsal root ganglion (DRG) also expressed low levels of GDNF mRNA. Two days after nerve transection, GDNF mRNA levels increased dramatically in the sciatic nerve. Overall, GDNF mRNA expression was significantly higher in peripheral organs than in neuronal tissues. Expression of either GDNF mRNA isoform in insect cells resulted in the production of indistinguishable mature GDNF polypeptides. Purified recombinant GDNF promoted neurite outgrowth and survival of embryonic chick sympathetic neurons. GDNF produced robust bundle-like, fasciculated outgrowth from chick sympathetic ganglion explants. Although GDNF displayed only low activity on survival of newborn rat SCG neurons, this protein was found to increase the expression of vasoactive intestinal peptide and preprotachykinin-A mRNAs in cultured SCG neurons. GDNF also promoted survival of about half of the neurons in embryonic chick nodose ganglion and a small subpopulation of embryonic sensory neurons in chick dorsal root and rat trigeminal ganglia. Embryonic chick sympathetic neurons expressed receptors for GDNF with Kd 1-5 x 10(-9) M, as measured by saturation and displacement binding assays. Our findings indicate GDNF is a new neurotrophic factor for developing peripheral neurons and suggest possible non-neuronal roles for GDNF in the developing reproductive system.
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PMID:Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons. 779 Mar 68

Light chain gene rearrangement during mammalian pre-B differentiation generally occurs in an orderly manner, beginning with kappa genes and proceeding through lambda genes. We have previously shown that human pre-B cell differentiation in vitro leads to a skewing toward lambda expression, resulting in a higher percentage of lambda+ cells than kappa+ cells. We now report that the multifunctional polypeptide transforming growth factor-beta (TGF-beta) exerts a selective inhibitory effect on the acquisition of cell surface lambda light chains during in vitro differentiation of normal human pre-B cells, giving rise to a balanced ratio (approximately 1:1) of kappa+ to lambda+ cells that resembles what normally exists in vivo. The TGF-beta effect was ablated using a neutralizing anti-TGF-beta antiserum and TGF-beta had no significant effect on the acquisition of kappa or surrogate light chains. Experiments using highly enriched pre-B cells (90-95% cytoplasmic mu+) suggested that the TGF-beta effect was directly on the pre-B cell or the pre-B cell to mu+/lambda+ immature B cell transition. The following peptides, cytokines, and antibodies had no effect on light chain acquisition or expression: substance P, vasoactive intestinal peptide, leu/met enkephalin, IL-1, IL-4, IL-7, anti-class II MHC, anti-CD24, anti-CD40, and the CD10 inhibitor phosphoramidon. A selective regulatory role for TGF-beta on normal human B cell development in the bone marrow microenvironment is suggested by these results.
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PMID:Transforming growth factor-beta regulates normal human pre-B cell differentiation. 815 4

The tachykinins are a family of neuropeptides that share a common carboxyl terminus. Substance P (SP) and neurokinin-A (NK-A) are derived from the preprotachykinin l gene. Although SP and NK-A can bind to either NK-1, NK-2, or NK-3 receptors (R), they have preferences for NK-1R and NK-2R, respectively. We have reported that SP stimulates erythroid (E) (burst-forming unit [BFU]-E and colony-forming unit [CFU]-E) and myeloid (CFU-granulocyte-macrophage [GM]) progenitors partly through the induction of growth factors. We have now investigated the hematopoietic effects of NK-A using short-term bone marrow (BM) cultures and found that NK-A (10(-7) to 10(-12) mol/L) inhibits CFU-GM proliferation but stimulates erythroid progenitors. Release of soluble factors by the stroma appears to mediate the inhibition because direct contact with the stroma was not required. We have found that NK-A, through NK-2-like receptors induces increased levels of macrophage inflammatory protein-1 alpha (MIP-1 alpha) and transforming growth factor-beta (TGF-beta) (transcriptional and posttranscriptional) in BM stroma. Clonogenic assays with NK-A (10(-9) mol/L) and either anti-MIP-1 alpha or anti-TGF- beta 1 indicate that these cytokines partly contribute to the inhibition, suggesting that these two negative hematopoietic regulators exert part of the inhibition by NK-A on CFU-GM. The findings of two closely related neuropeptides, derived from the same gene, exerting opposite effects on myeloid colonies suggest that neuropeptides, by themselves could be important factors in hematopoietic regulation.
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PMID:Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma. 870 7

The evidence for the integration of the submandibular gland (SMG) into the neuroimmunoregulatory network has been reviewed. In laboratory rodents, factors extracted from the SMG were shown to stimulate lymphocyte proliferation, to affect the weight of the thymus, spleen and lymph nodes and to induce immunosuppression in several in vivo animal models. The SMG produces significant quantities of nerve growth factor (NGF), epidermal growth factor (EGF), transforming growth factor-beta and kallikreins, which are secreted into the saliva and affect immune and mucosal tissues and nerve endings in the gastrointestinal tract. These factors play a role in regulating mucosal immuno/inflammatory response and in regeneration and healing. The major salivary glands also produce antimicrobial proteins and secretory IgA antibodies which are essential factors in mucosal host defense. SMG-derived NGF, EGF and glandular kallikrein are delivered into the bloodstream where they may act as important systemic immunoregulators and also have major regulatory influences on the central neuroendocrine system. There is evidence to indicate that EGF is involved in the regulation of gonadal function. Growth hormone, prolactin, androgens, thyroid hormone and corticosteroids regulate protein synthesis in the SMG, whereas secretory activity is regulated by sympathetic (alpha- and beta-adrenergic) parasympathetic (muscarinic) and peptidergic (substance P and vasoactive intestinal peptide) nerve fibers. Fluid and electrolyte secretion is promoted by parasympathetic, whereas protein secretion is stimulated by sympathetic nerve impulses. Steroid hormones and cytokines (interleukin-1 alpha, -beta, tumor necrosis factor, interferon-gamma) have a major regulatory influence on protein secretion, including the secretion of immunoglobulin into the saliva. The SMG interacts with the mucosal and systemic compartments of the immune system, with the central and peripheral nervous systems, with the pituitary gland, and with peripheral endocrine organs. These interactions enable the SMG to exert regulatory influences on immune/inflammatory reactions in the gastrointestinal tract, in the lungs, and possibly elsewhere. It is suggested that these functions make this gland a key regulatory organ in the neuroimmunoregulatory network. Evidence is increasing that the major salivary glands fulfill similar functions in other species, including humans.
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PMID:The submandibular gland: a key organ in the neuro-immuno-regulatory network? 896 48

Trefoil peptides are a family of small proteins expressed by goblet cells that are secreted onto the apical gastrointestinal mucosal surface, where they are present in high concentrations. These peptides appear to both protect the epithelium and promote healing after injury. However, the factors regulating the expression and secretion of these proteins contributing to mucosal defense have not been characterized. To determine the mechanisms controlling production of trefoil peptides, the human colon cancer-derived model cell line HT-29 was exposed to a variety of potential secretagogues. Expression and secretion of human intestinal trefoil factor (hITF) as well as the intestinal apomucin MUC2 were assessed by Northern and Western blot analysis. Carbachol, an analog of acetylcholine, and the neuroendocrine peptides somatostatin and vasoactive intestinal polypeptide (VIP) stimulated increased expression of hITF mRNA within 5 min. These same factors stimulated parallel secretion of the hITF peptide, with maximal stimulation observed at concentrations ranging from 10(-6) M (carbachol and somatostatin) to 10(-7) M (VIP). Expression and secretion of hITF in response to carbachol, VIP, and somatostatin was independent of production of apomucin. hITF was not regulated by other neuroendocrine transmitters including histamine and substance P. Similarly, hITF expression and secretion was not modulated by peptide growth factors (epidermal growth factor, transforming growth factor-beta, and keratinocyte growth factor), cytokines [interleukin (IL)-1 beta, IL-2, IL-7, and IL-11], or arachidonic acid metabolites (prostaglandin E1/E2 and leukotriene B4). In conclusion, trefoil peptides appear to be integrated into mechanisms of mucosal defense and repair through the enteric neuroendocrine system and independent of the classical mucosal immune cytokine network.
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PMID:Trefoil peptide expression and secretion is regulated by neuropeptides and acetylcholine. 927 13

In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(TGF-beta); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin-1alpha (IL-1alpha), IL-1beta, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 microg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-beta, laminin, IL-1alpha, and IL-1betadid not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
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PMID:Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea. 929 69

Following brain injury, astrocytes express receptors for cytokines and neuropeptides and secrete several regulatory mediators that have a well established role in inflammation, immunity, and tissue development or repair. To elucidate the role of substance P (SP), a neurotransmitter peptide of the tachykinin family, in inducing astrocyte secretory activities, we have examined the expression of SP receptors and the functional consequences of their activation in cultured astrocytes from the human embryonic brain or spinal cord. Radioligand binding studies revealed that only one type of SP receptors, the high affinity NK-1 receptor, was present on human astrocytes and that spinal cord astrocytes expressed about 6 times as many SP binding sites as brain astrocytes. Following SP treatment, a substantial inositol phosphate formation was observed in spinal cord astrocytes only. Stimulation of spinal cord astrocytes with SP alone did not induce secretion of cytokines [interleukin-6 (IL-6), granulocyte-macrophage-CSF, macrophage chemoattractant protein-1 or leukemia inhibitory factor] or prostaglandin E2 (PGE2). Interestingly, however, SP selectively potentiated the inducing effect of IL-1beta on IL-6 and PGE2 secretion by spinal cord astrocytes without affecting the IL-1-beta-evoked secretion of other cytokines. SP also enhanced the small inducing effect of tumor necrosis factor-alpha (TNF-alpha) on IL-6 and PGE2 secretion and that of transforming growth factor-beta on PGE2 secretion. These results suggest that SP can enhance immunoregulatory and neurotrophic astroglial functions mediated by IL-6 and PGE2 by acting in concert with a set of cytokines whose cerebral expression has been reported during development and in a variety of diseases.
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PMID:Functional characterization of substance P receptors on cultured human spinal cord astrocytes: synergism of substance P with cytokines in inducing interleukin-6 and prostaglandin E2 production. 933 33

Mesenchymal cell migration and replication are central biologic events involved in atherosclerosis and lung and hepatic fibrosis. Tissue repair and fibrosis are thought to be regulated by growth regulatory molecules, comprising both stimulators and inhibitors of mesenchymal cell functions, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), fibroblast growth factors, and several neuropeptides such as substance P. Secretoneurin (SN), a novel 33-amino acid neuropeptide derived from secretogranin II (chromogranin C), is widely distributed in the central and peripheral nervous and neuroendocrine systems, including afferent C-fibers, and can be released in the periphery by capsaicin. Recently, we reported that SN triggers the selective migration of human monocytes and fibroblasts in vitro, implicating its involvement in inflammatory responses. We report herein that SN stimulates specific migration (maximal response at 10(-10) M) of cultured arterial smooth muscle cells (SMCs), originating from rat thoracic aorta, and initiates DNA synthesis and SMC growth (BrdU incorporation, MTT test) with a maximum at 10(-8) M SN to a similar extent as observed by PDGF. Both functional activities of SN were inhibited by specific anti-SN immunoglobulins (dilution, 1:1000), and furthermore, a trypsinized SN peptide (10(-8) M) was unable to provoke biologic effects. Our studies suggest that SN functions as a regulatory peptide to modulate SMC migration and proliferation, which in conjunction with other factors could serve to aggravate and accelerate the development of atherosclerotic or restenotic lesions at sites of vascular injury.
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PMID:Response of vascular smooth muscle cells to the neuropeptide secretoneurin. A functional role for migration and proliferation in vitro. 935 68


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