Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The granulomas of mice infected with Schistosoma mansoni for 8 wk have macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has no known function. To uncover the possible significance of SOM produced within this granulomatous inflammation, we sought SOM receptors on distinct cellular components of the granuloma to identify cells targeted for SOM action. [125I]SOM 1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly. Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide, a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1-28, substance P, and vasoactive intestinal peptide did not. The SOM receptor localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5 and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6) did not affect IL-5 production. Octreotide administered to animals in vivo decreased the intensity of the granulomatous response. Thus, some granuloma T cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may participate in regulation of the granulomatous response by modulating the secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics the action of SOM on the immune system.
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PMID:Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. 135 73

Inflammatory cells secrete some neuropeptides that function as immunomodulators. Somatostatin has immunoregulatory properties. It is unknown whether immune cells make somatostatin. Intricate intercellular communications govern the granulomas of murine Schistosoma mansoni. These granulomas synthesize several neuropeptides. Thus, it was determined whether somatostatin is in these inflammatory lesions. Granulomas, which were isolated from the livers of infected mice, contained somatostatin 1-14 as shown by radioimmunoassay and chromatography. Immunostaining localized immunoreactive somatostatin and pre-prosomatostatin to granuloma macrophages. Granuloma macrophages cultured in vitro released immunoreactive somatostatin. Calcium ionophore A23187, which promotes macrophage secretion, increased somatostatin in the culture supernatants. Thus, the granulomas have a molecule with somatostatin 1-14-like properties that is possibly a secretory product of the granuloma macrophage.
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PMID:Macrophages within the granulomas of murine Schistosoma mansoni are a source of a somatostatin 1-14-like molecule. 197 99

Immunocytochemical techniques applied to sections and whole-mount preparations of cercariae from two species of trematodes, Trichobilharzia ocellata and Schistosoma mansoni, revealed the occurrence of immunoreactivity (IR) to several neurosubstances in the nervous system (NS). Immunostaining was localized in cerebral ganglia, in the main commissure, in anterior and posterior nerve trunks, as well as in a pair of nerve fibres running along the tail. In T. ocellata, immunoreactivity (IR) was observed with antisera raised against: glutamate, FMRFamide, catch-relaxing peptide (CARP), small cardiac peptide B (SCPB), arg-vasotocin (AVT), arg-vasopressin (AVP), and substance P. In S. mansoni antisera raised against glutamate, FMRFamide, CARP, SCPB, alpha-caudodorsal cell peptides (alpha-CDCP), and cholecystokinin (CCK) showed neuronal IR. With the other 51 antisera tested no IR was observed. With anti-APGWamide, IR was observed outside the NS in cells of the wall of the daughter sporocyst and in flame cells of cercariae of T. ocellata. IR to FMRFamide was present in the escape glands of the intrasporocystic cercariae of T. ocellata and S. mansoni. IR to somatostatin was observed in subtegumental parenchymal cells of cercariae of S. mansoni. IR to met-enkephalin was present in cells of the cercarial embryos and in undifferentiated cells in developing cercariae. Trematodes are, together with cestodes, phylogenetically the oldest classes in which glutamate-like material and immunopositivity to a number of neuropeptides isolated from invertebrates has been demonstrated. The results are discussed in relation to immunocytochemical data obtained for other platyhelminths, to endogenous functions of the immunopositive materials, and to their possible role in parasite-host interactions.
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PMID:Immunocytochemical study on biologically active neurosubstances in daughter sporocysts and cercariae of Trichobilharzia ocellata and Schistosoma mansoni. 802 56

The role of somatostatin (SRIF) in controlling the granulomatous inflammatory response to infection with the parasite Schistosoma mansoni was explored in mice. The murine granulomas contain SRIF-14. Immunoreactive SRIF and prepro SRIF localize in the cytoplasmic granules of macrophages within the granulomas. The granulomas contain mRNA for prepro SRIF and are not innervated. The production of SRIF by the inflammatory cells appears to be inducible. The granulomas contain mRNA for the SRIF receptors sst2A and sst2B, which are expressed mainly on CD4- T lymphocytes and bind SRIF-14 with high affinity. Antigens from the schistosome eggs stimulate granuloma T lymphocytes to produce cytokines. Interferon-gamma (IFN-gamma) is one such cytokine made by CD4+ T lymphocytes. SRIF-14 suppresses antigen-induced IFN-gamma production from granuloma cells, and this effect is blocked by anti-sst2 antibody. SRIF was shown to inhibit IFN-gamma-induced immunoglobulin G2a (lgG2a) synthesis in murine schistosomiasis. SRIF also blocks substance P (SP)-stimulated IFN-gamma and lgG2a secretion. Schistosome-infected animals treated with the SRIF analog octreotide form smaller granulomas that secrete substantially less IFN-gamma and lgG2a. Unpublished observations suggest that SRIF does not modulate schistosome egg antigen- or concanavalin A-stimulated granuloma lymphocyte proliferation in murine schistosomiasis. In conclusion, SRIF may be an important factor in the control of the granulomatous inflammatory response in murine schistosomiasis.
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PMID:Granulomas in murine schistosomiasis mansoni have a somatostatin immunoregulatory circuit. 876 93

Substance P (SP) and somatostatin (SOM) are made at mucosal surfaces and sites of inflammation. There is a SP/SOM immunoregulatory circuit that modulates the IFN-gamma response in murine schistosomiasis. SP enhances, while SOM decreases, IFN-gamma secretion. Various inflammatory mediators induce macrophages to make SOM, but no known factor limits this expression. It was discovered that SP regulates SOM synthesis. Splenocytes from normal, uninfected mice cultured with LPS, IFN-gamma, or IL-10 for 4 h strongly expressed SOM mRNA, but failed to do so in the presence of SP. The inhibition with 10(-9) M SP was > 85% shown by quantitative PCR. Also, splenocyte SOM content decreased from 1048 +/- 275 to < 10 pg/4 x 10(8) cells following SP exposure. Immunohistochemistry identified SOM solely within splenic macrophages following cytokine stimulation. Mice infected with Schistosoma mansoni form granulomas in the liver and intestines resulting from deposition of parasite eggs in these organs. The granulomas contain macrophages that make SOM constitutively. SP at 10(-8) M decreased SOM mRNA expression > 90% in dispersed granuloma cells cultured for 4 h or longer. Specific SP receptor antagonists blocked SP suppression of SOM expression in splenocytes and dispersed granuloma cells, showing that an authentic SP receptor mediated the regulation. Additional studies revealed that IL-4 antagonized the SP effect in the spleen. It is concluded that in granulomas and splenocytes from mice with schistosomiasis and in splenocytes from uninfected animals that 1) SP inhibits macrophage SOM induction and ongoing expression at the mRNA and protein levels acting through the SP receptor, and 2) IL-4 can antagonizes this SP effect.
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PMID:Substance P regulates somatostatin expression in inflammation. 983 21

Communication and reciprocal regulation between the nervous, endocrine and immune systems are essential for the stability of the organism. Among others, cytokines, hormones and neuropeptides have been identified as signalling molecules mediating the communication between the three systems. This review focuses on the role of the neuropeptide somatostatin as an intersystem signalling molecule, with emphasis on the immune system. Somatostatin down-modulates a number of immune functions, among others lymphocyte proliferation, immunoglobulin production and the release of proinflammatory cytokines such as IFN-g. Systemic or local treatment with somatostatin or somatostatin analogues has been shown to be beneficial in a number of in vivo models of autoimmune disease and chronic inflammation. In many of these models somatostatin appears to antagonise the effects of another neuropeptide, substance P. A somatostatin-substance P immunoregulatory circuit has been proposed to operate within murine Schistosoma mansoni-induced granulomas. In this review we extend the model of the somatostatin-substance P immunoregulatory circuit to include data derived from other biological systems, and those relying on human clinical situations. In addition, we present a hypothesis on the regulation of the default class of immune response within a tissue, based on the local balance of pro-and anti-inflammatory neuropeptides.
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PMID:Somatostatin and somatostatin receptors in the immune system: a review. 1090 95

This review explores the possible modulatory role of the neuropeptide somatostatin in the outcome of Schistosoma-caused morbidity in man. Somatostatin could play an important role in Schistosoma mansoni-man interactions via its influence on intersystem signalling; therapeutically, via its direct effect on Schistosoma-caused morbidity (fibrosis, granuloma size, portal hypertension, variceal bleeding); and via immunomodulation of Schistosoma-induced inflammatory responses in the liver and intestines. In schistosomiasis-endemic regions two interesting patterns of infection emerge. First, the intensity of infection is higher in children than in adults; secondly, at any given time, only a fraction of Schistosoma-infected individuals develop Symmer's pipe-stem fibrosis. These morbidity patterns cannot be explained on the basis of acquired immunity alone. Somatostatin has an inhibitory effect on hormone, immune and physiological body functions like growth hormone secretion, Interferon (IFN) gamma production, collagen I and III formation and hepatic stellate cell activation. Levels of somatostatin secreted endogenously by man upon the onset of Schistosoma infection may be one factor regulating the activity of the above, and thereby fibrosis in the host. The neuropeptide hormone somatostatin may determine pre-disposition to Schistosoma-caused morbidity.
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PMID:The role of somatostatin in schistosomiasis: a basis for immunomodulation in host-parasite interactions? 1155 24

The neuropeptide hormone somatostatin is used to treat bleeding oesophageal varices and to reduce portal pressure, and can prevent progression to severe fibrosis in chronic liver disease. We believe that somatostatin can also have therapeutic potential against schistosomiasis, based on recent observations that severe morbidity symptoms are associated with low levels of host somatostatin in patients infected with Schistosoma mansoni. The administration of exogenous doses of this neuropeptide could therefore alleviate the pathology caused by schistosomiasis.
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PMID:Does the neuropeptide somatostatin have therapeutic potential against schistosomiasis? 1237 48

In recent years, cases of severe morbidity (fibrosis, haematemesis, hepatosplenomegaly, ascites) caused to Schistosoma mansoni infections are on the rise in Northern Senegal. The neuropeptide somatostatin is reported to decrease portal pressure, control variceal bleeding and fibrosis, and reduce Schistosoma-caused clinical morbidity in the rodent model. The aim of this study was to delineate the role of somatostatin in S. mansoni-caused pathogenesis, by studying host levels of somatostatin in the peripheral blood of uninfected and S. mansoni-infected individuals. Subjects from the district dispensary at Richard Toll, in the Medical Region of Saint-Louis, Senegal, infected with S. mansoni and suffering from severe morbidity were selected. A separate group consisted of individuals resident in the same region but uninfected at the time of the study. Significantly lower somatostatin levels were detected in severe morbidity patients, compared with the exposed but uninfected subjects. In patients with schistosomiasis physiological levels of somatostatin may determine disposition of particular individuals towards severe morbidity, as opposed to others. Host pathology can thus be alleviated by the therapeutic ability of somatostatin to treat bleeding oesophageal varices, reduce portal pressure and prevent progression to severe fibrosis.
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PMID:Lower levels of the circulating neuropeptide somatostatin in Schistosoma mansoni infected patients may have pathological significance. 1253 48

Intestinal schistosomiasis is accompanied by motility-related dysfunctions but the underlying mechanisms are not well-known. Therefore, the presence and effects on intestinal contractility of somatostatin (SOM) and its receptor, SSTR2A, were investigated in the ileum of normal and infected mice. The distribution of SOM and SSTR2A was visualized using immunocytochemistry. Radioimmunoassay combined with oogram studies was performed to determine SOM levels and contractility measurements were determined in organ bath experiments. Schistosomiasis resulted in a significant decrease in somatostatin-positive endocrine cells, whereas the number of somatostatin-immunoreactive (IR) neuronal cell bodies did not change. From 8 weeks postinfection onwards, an increase was noted in somatostatin-IR nerve fibres in both villi and granulomas. The staining intensity for SSTR2A, expressed in somatostatin-negative myenteric cholinergic neurones, increased during infection suggesting an upregulation of this receptor. SOM levels were negatively correlated with the number of eggs during the acute phase, and were elevated during the chronic phase. Pharmacological experiments revealed that schistosomiasis diminished the inhibitory effect of SOM on neurogenic contractions. We can conclude that schistosomiasis influences the distribution and expression levels of SOM and SSTR2A in the murine ileum, which might explain the changed motility pattern.
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PMID:Effects of Schistosoma mansoni infection on somatostatin and somatostatin receptor 2A expression in mouse ileum. 1268 Sep 14


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