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)

Lymphocytes from peripheral blood of rainbow trout are put in the presence of increasing concentrations of substance P (SP) and somatostatin (SOM). We have shown that SP stimulates and SOM inhibits lymphoproliferation and that the effects are dose dependent. These results suggest that SP and SOM receptors may exist on fish peripheral blood lymphocytes. When cells are stimulated by PHA or LPS, the presence of SP enhances the response to PHA whereas it only modifies the response to LPS to a slight extent. The presence of SOM inhibits PHA- or LPS-induced stimulation. The inhibition of the proliferation is higher in the case of LPS-stimulated cells. These results suggest that there is an unequal distribution of neuropeptide receptors among the various lymphocyte subpopulations.
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PMID:In vitro effects of substance P and somatostatin on lymphoproliferation in rainbow trout (Salmo gairdneri). 137 68

Interleukin-6 (IL-6) is an inflammatory cytokine that stimulates T-cell activation and B-cell differentiation. We recently reported that picomolar concentrations of IL-6 stimulated PRL, GH, and LH release in vitro. These data suggested that IL-6 may function as a hypothalamic releasing factor for anterior pituitary hormones. Medial basal hypothalami (MBH) were incubated for 60-90 min in Krebs-Ringer bicarbonate buffer supplemented with 0.025% BSA, and the conditioned medium was assayed for IL-6 concentrations by the 7TD1 cell growth factor assay. It was found that MBH released IL-6 in vitro. Although depolarizing concentrations of K+ (56 mM) did not increase IL-6 release, somatostatin release from the MBH was increased significantly. The bacterial endotoxin lipopolysaccharide (LPS; 1-100 ng/ml) induced significant increases in IL-6 release from the MBH. The presence of IL-6 in the hypothalamus suggested a possible role for this cytokine in the regulation of neuropeptide release; however, the release of somatostatin was not affected by 20 ng/ml IL-6. Comparison studies of neural and neuroendocrine tissues revealed that the anterior and posterior pituitaries released larger amounts of bioactive IL-6 than the MBH or parietal cortex during a 4-h incubation; induction of IL-6 release by endotoxin occurred only in the anterior pituitary and hypothalamus. IL-6 mRNA was detectable in the MBH and anterior pituitary tissue after a 4-h incubation; however, no IL-6 mRNA was detectable in freshly isolated tissues. LPS (100 ng/ml) and (Bu)2cAMP (1 mM) increased IL-6 mRNA accumulation in and IL-6 release from the MBH and anterior pituitary. These data suggest that the MBH synthesizes and releases IL-6 via a nonneuronal source in vitro.
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PMID:Endotoxin-induced release of interleukin-6 from rat medial basal hypothalami. 197 93

Conditions are described for performing mitogen (Concanavalin A, Con A; lipopolysaccharide, LPS) and mixed lymphocyte reaction (MLR) cultures using serum-free medium. The effects of exogenously adding several gastrointestinal regulatory peptides (beta-endorphin, substance P, met-enkephalin, vasoactive intestinal peptide, bombesin and somatostatin) on the incorporation of 3H-methyl-thymidine was determined. It was observed that mitogen stimulation of lymph node cells with Con A was inhibited (70% of control) by vasoactive intestinal peptide (VIP) but spleen cells stimulated by LPS were insensitive to immunomodulation (98% of control). The ability of VIP to inhibit Con A induced thymidine incorporation was concentration dependent (10(-6) to 10(-18) M) and was not attributable to kinetic shifts or cell toxicity. None of the other tested neuropeptides affected Con A or LPS induced blastogenesis. MLR cultures were inhibited by VIP, beta-endorphin and somatostatin in a biphasic manner with maximal inhibition observed at 10(-8) to 10(-12) M. Both substance P and bombesin exhibited slight immunoenhancing properties at 10(-14) to 10(-18) M. Met-enkephalin was ineffective as an immunomodulator of MLR cultures. The utility of using serum-free medium in identifying neuropeptides with immunomodulatory properties are discussed.
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PMID:Gastrointestinal regulatory peptides modulate mouse lymphocyte functions under serum-free conditions in vitro. 242 44

To identify brain neurons that participate in the acute phase response, rat brains were examined immunocytochemically for Fos protein following the intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS). Two to three hours after the injection of LPS, 150 micrograms/kg body weight, to adult male Long-Evans rats, a consistent anatomic pattern of Fos immunostained cell nuclei is seen. In the brain stem, prominant Fos immunostaining is induced in tyrosine hydroxylase immunoreactive neurons of the caudal ventral-lateral medulla (the A1 cell group), in both tyrosine hydroxylase positive and negative neurons of nu. tractus solitarius, in the parabrachial nu., and in a few neurons of the locus ceruleus. In the hypothalamus, endotoxin induces Fos expression in magnocellular neurons of the paraventricular and supraoptic nuclei and internuclear cell groups. A higher percentage of oxytocin-immunoreactive cells is double labeled for Fos nuclear immunostaining than vasopressin-immunoreactive cells. A minority of somatostatin immunoreactive periventricular hypothalamic neurons are Fos positive. Other hypothalamic nuclei that contain endotoxin-induced Fos nuclear immunostaining include the parvocellular neurons of the paraventricular nu., the dorsomedial and arcuate nuclei, the lateral hypothalamus, the dorsal hypothalamic area (zona incerta), and the median nucleus of the preoptic area. LPS induces numerous Fos-positive neurons in regions known to respond to a variety of stressful stimuli; these regions include the preoptic area, bed nucleus of the stria terminalis, lateral septum, and the central and medial nuclei of the amygdala. Moreover, Fos nuclear immunostaining is seen in neurons of circumventricular organs: the organum vasculosum of the lamina terminalis, the subfornical organ, and the area postrema. The maximum intensity of Fos nuclear immunostaining occurs 2-3 h after endotoxin administration and declines thereafter. It is attenuated by pretreatment with indomethacin, 25 mg/kg body weight Sc, or dexamethasone, 1 mg/kg IP. These observations are consistent with the participation of a variety of brain neuronal systems in the acute phase response and elucidate the functional neuroanatomy of that response at the cellular level.
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PMID:Anatomic patterns of Fos immunostaining in rat brain following systemic endotoxin administration. 771 98

Recent studies have shown that somatostatin modulates lymphocyte function, but the effects of somatostatin on macrophage function are not clearly defined. In the present study, peritoneal macrophages (Mluminal diameter) obtained from male rats were treated in vitro with somatostatin or octreotide and their effects on the release of hydrogen peroxide (H2O2), nitrite, and tumor necrosis factor (TNF) determined. Macrophages treated with somatostatin (10(-9) M to 10(-7) M) or octreotide (10(-8) M and 10(-7) M) released significantly greater amounts of PMA-stimulated H2O2 than did the untreated controls. In addition, 10(-9) M of somatostatin significantly enhanced PMA-stimulated H2O2 release by LPS-treated Mluminal diameter. Octreotide had no effect on H2O2 release by LPS-treated Mluminal diameter. At concentrations of 10(-14) M, 10(-13) M, or greater than 10(-8) M, somatostatin or octreotide suppressed nitrite release by Mluminal diameter. Somatostatin or octreotide did not affect nitrite release by LPS-treated Mluminal diameter. On the other hand, Mluminal diameter treated with 10(-11) M of somatostatin or octreotide released greater amounts of TNF than did the untreated controls. In contrast, TNF release by Mluminal diameter treated with 10(-9) M to 10(-5) M of somatostatin or 10(-7) M to 10(-5) M of octreotide was less than that of the controls. Anti-TNF antibody (1:1000) caused a reduction in the release of H2O2 and nitrite. These findings demonstrate that somatostatin and octreotide modulate the release of H2O2, nitric oxide, and TNF by Mluminal diameter depending on the concentration of hormones used.
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PMID:Somatostatin and macrophage function: modulation of hydrogen peroxide, nitric oxide and tumor necrosis factor release. 857 Aug 54

In the present study, we examined the in vitro and in vivo modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of AtT-20 mouse pituitary adenoma cells for 24 h with neuroendocrine mediators of stress such as CRF and catecholamines produced dose-dependent increases in cAMP production and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increases in [125I]IL-1 alpha binding. Furthermore, in keeping with the effects of stress mediators to up-regulate IL-1 receptors in AtT-20 cells, ether-laparotomy stress in mice resulted in a significant increase in [125I]IL-1 alpha binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether-laparotomy stress. Next, we investigated the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following endotoxin treatment. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis, and spleen) at 2-6 h after a single LPS injection (30 micrograms LPS/mouse); however, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding in the pituitary gland, liver, spleen, and testis was significantly decreased at 2 h following a single administration of both low (30 micrograms LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1 alpha binding in the hippocampus was not significantly altered at 2 h by low dose of LPS and was significantly decreased by high-dose administration of LPS (300 micrograms/mouse). Following two LPS injections (at 0 and 12 h), dramatic increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen, and testis were observed at 2 h after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of 30 micrograms LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to stress and infection.
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PMID:Interleukin-1 receptors in the brain-endocrine-immune axis. Modulation by stress and infection. 859 15

The immunosuppressor effects of the widely distributed neuropeptide somatostatin were examined on purified peripheral blood human monocytes. Somatostatin, at concentrations thought to be physiologic (10(-10)-10(-7) M), regulated monocyte/macrophage responses to (LPS) stimulation, as reflected by interleukin production. In particular, somatostatin had direct inhibitory effects on TNF-alpha, IL-1 beta, and IL-6 secretion by LPS-activated monocytes, while the decrease on IL-8 synthesis was modulated mainly by the action of somatostatin on TNF-alpha and IL-1 beta. In fact, the addition of these two inflammatory cytokines to the monocyte culture medium was able to induce IL-8 expression, as demonstrated by mRNA analysis, also in presence of the neuropeptide. Although somatostatin affected IL-8 production in an indirect way, it suppressed directly the chemotactic response of neutrophils to IL-8. Finally, somatostatin downregulation of monocyte activation was confirmed by the decrease of HLA-DR expression on cell plasma membranes (52% versus 33%). Our results confirm that somatostatin exerts preferential effects on the suppression of immunoreactions by modulating cytokine production and activity.
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PMID:Modulation of cytokine production in activated human monocytes by somatostatin. 892 6

In the present study, we have investigated the effect in vitro of gastrin-releasing peptide (GRP, 10(-10) M), neuropeptide Y (NPY, 10(-10) M), somatostatin (10(-10) M) and vasoactive intestinal peptide (VIP, 10(-9) M) on the production of IL-1 beta, IL-6 and TNF alpha by peripheral whole blood cells from healthy young and old people. We have found that GRP, NPY, somatostatin and VIP stimulated the production of IL-1 beta in old subjects, and NPY, somatostatin and VIP in young ones. In addition, the production of IL-6 was enhanced by GRP, NPY and VIP in young and old people. The TNF alpha production was stimulated by NPY and somatostatin in young subjects, and by NPY, somatostatin and VIP in old ones, whereas GRP produced a decrease of TNF alpha in young persons. GRP in old subjects and VIP in young and old subjects stimulated in a great degree the LPS-induced IL-6 production by whole blood cells. On the contrary, GRP and VIP inhibited highly the LPS-induced TNF alpha production in young controls. Our results show that these neuropeptides, when added to whole blood cells at physiological concentrations, are able to stimulate the production of IL-1 beta, IL-6 and TNF alpha in a differential way according to the subject age.
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PMID:Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha production by whole blood cells from healthy young and old subjects. 898 99

Somatostatin (SOM) is a 14-amino acid cyclic peptide that regulates granulomatous inflammation. SOM inhibits the release of IFN-gamma from murine granuloma T cells that express SOM receptors. SOM is synthesized as preprosomatostatin (ppSOM), a precursor peptide that is cleaved to release active SOM. In this paper, we demonstrate that granuloma cells express mRNA for this important immunoregulator, and that inflammatory mediators rapidly induce ppSOM mRNA in the splenocytes of uninfected, normal (NL) mice. We developed a sensitive, quantitative PCR assay that measures ppSOM mRNA down to 100 transcripts per microg of total RNA. Dispersed granuloma cells expressed authentic ppSOM mRNA as determined by RT-PCR and cDNA sequencing. The PCR assay readily detected ppSOM mRNA in splenocytes isolated from schistosome-infected mice, but not in splenocytes from NL mice. Splenic ppSOM mRNA expression correlated with the onset of parasite egg deposition and granuloma formation. A 4-h in vitro stimulation with LPS, rIL-10, rIFN-gamma, rTNF-alpha, prostaglandin E2, or dibutyryl cAMP induced ppSOM mRNA in NL splenocytes that otherwise lacked this transcript. Splenocytes from severe combined immunodeficient or recombination activating gene 1-deficient mice expressed ppSOM after exposure to rIL-10, suggesting that neither T nor B cells are necessary for ppSOM mRNA induction. A survey of cell lines demonstrated expression of ppSOM mRNA by P388D1 and J774A.1 macrophage-like cells. These data suggest that SOM, which is probably derived from macrophages, is an inducible component of the innate immune system that regulates T cell IFN-gamma production.
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PMID:Preprosomatostatin messenger RNA is expressed by inflammatory cells and induced by inflammatory mediators and cytokines. 955 8

Murine schistosomiasis mansoni is a parasitic disease in which flukes living in the portal vein of the host produce ova that deposit in the liver and intestines. In these organs, ova release antigens that induce chronic, focal granulomatous inflammation. IFN-gamma is an inflammatory cytokine important in macrophage activation and B-cell differentiation. A substance P (SP)/somatostatin (SOM) neurokine immunoregulatory circuit controls IFN-gamma production in schistosome granulomas. SP stimulates, while SOM inhibits IFN-gamma release, modulating IFN-gamma-dependent circuitry. SP and SOM function through interaction with authentic SP and SOM receptors located on granuloma T cells. Also, the granulomas produce authentic SP and SOM14, as evidenced by the presence of mRNA and product. The granulomas have no nerves. This, and other data suggest that the inflammatory cells make these neurokines. Granuloma macrophages produce SOM. Macrophages from various sources express SOM mRNA in response to LPS, IFN-gamma, IL-10 or several other inflammatory mediators. Thus, the inflammation of murine schistosomiasis has a complete SP/SOM immunoregulatory circuit, which in turn is subject to immunoregulation.
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PMID:The substance P and somatostatin interferon-gamma immunoregulatory circuit. 962 80


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