Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty percent of the world's population is infected with Helicobacter pylori; however, treatment has been insufficient to eradicate the organisms due to rising antibiotic resistance. Helicobacter infection is characterized by induction of a T helper 1 lymphocyte (Th1) immune response, hypergastrinemia, and suppressed tissue somatostatin (SOM) levels. However, the mechanism by which the immune response regulates acid secretion is not known. We show here that treatment with IFN-gamma, a Th1 cytokine, was sufficient to induce gastritis, increase gastrin, and decrease SOM levels within 7 days. In contrast, the T helper 2 lymphocyte cytokine IL-4 increased SOM levels and effectively suppressed gastrin expression and secretion. This result demonstrated reciprocal regulation of acid regulatory peptides by immune modulators. IL-4 pretreatment prevented gastritis in infected wild-type but not in SOM null mice. Thus, the ability of IL-4 to oppose a Th1-mediated infection required SOM. Immunofluorescence was used to document the presence of IL-4 receptors on the gastric SOM-secreting cell (D cell). Moreover, IL-4 stimulated SOM release from primary D cell cultures. Treatment of mice chronically infected with Helicobacter felis for 2 mo with the SOM analogue octreotide resolved the inflammation. Thus, a mechanism by which IL-4 resolves inflammation in the stomach is by stimulating the release of SOM from gastric D cells.
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PMID:Treatment of Helicobacter gastritis with IL-4 requires somatostatin. 1455 68

During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcepsilonRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34(+) progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-gamma (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte-macrophage colony-stimulating factor, but not IL-4, interferon-gamma or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases.
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PMID:Neuropeptides activate human mast cell degranulation and chemokine production. 1792 33

The physiological processes leading to the expression of the resilient phenotype, which allow animals to maintain a relatively higher production level during infection, have been investigated in lambs from a closed flock selected for 40 generations for high fleece weight (HFW), but with higher FEC and worm burdens than their unselected control (C) flock run in parallel. After recovery from surgery to implant abomasal cannulae, eight parasite-naive lambs from each flock were infected intraruminally at 4.5 months-of-age with 50,000 Teladorsagia circumcincta L3. Blood, abomasal fluid and faecal samples were collected daily for measurement of serum gastrin and pepsinogen concentrations, blood eosinophils, abomasal pH and FEC. Four lambs from each flock were euthanased on Day 8 post-infection and the other four on Day 28 post-infection. At necropsy, abomasal contents and tissues were collected for worm counts, abomasal lymph nodes and fundic tissue for cytokine gene expression and fundic tissue for histopathology. Expression of resilience appeared to be age-dependent as there were no significant differences in either FEC or worm burden between lambs from the two flocks, unlike older HFW lambs in a previous study. Abomasal secretion did not differ between flocks. Histopathological changes were typical of parasitism: inflammatory cells, mainly eosinophils and lymphocytes, were numerous in nodular areas and there were fewer TGF-alpha positive parietal cells, many of which were vacuolated. By Day 28 p.i., globule leucocytes were present. Mucosal thickness was significantly greater on Day 8 than Day 28 p.i. (p=0.000) and in C than HFW lambs. There were fewer parietal cells on Day 28 than on Day 8 p.i. (p=0.003) for pooled data. Circulating eosinophil counts increased moderately in both groups, significantly less in the HFW lambs. Fewer tissue and blood eosinophils in the HFW than C group on Day 8 p.i. were consistent with cytokine gene expression patterns, particularly lower IL-5 levels. Worm count decreased by 90% by Day 28 p.i., along with declining tissue eosinophil counts and IL-13 gene expression and increasing IL-10 and IL-4 gene expression. Food intake was depressed less in the HFW lambs, suggesting that maintenance of appetite could be an important aspect of the physiological basis for resilience. Although the resilient phenotype was not apparent at the younger age, lesser effects on food intake, differences in ALN cytokine profiles and lower blood and tissue eosinophil numbers in the HFW lambs may lead to the expression of resilience when older.
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PMID:Effects of Teladorsagia (Ostertagia) circumcincta infection on lambs selected for high fleece weight. 1967 87

Host defense is an orchestrated response involving changes in the expression of receptors and release of mediators from both immune and structural cells. There is a growing recognition of the important role of proteolytic pathways for the protective immune response to enteric pathogens. Enteric nematode infection induces a type 2 immune response with polarization of macrophages toward the alternatively activated phenotype (M2). The Th2 cytokines, IL-4, and IL-13, induce a STAT6-dependent upregulation of the expression of the protease inhibitor, serpinB2, which protects macrophages from apoptosis. M2 are critical to worm clearance and a novel role for serpinB2 is its regulation of the chemokine, CCL2, which is necessary for monocyte and/or macrophage influx into small intestine during infection. There is a growing list of factors including immune (LPS, Th2 cytokines) as well as hormonal (gastrin, 5-HT) that are linked to increased expression of serpinB2. Thus, serpinB2 represents an immune regulated factor that has multiple roles in the intestinal mucosa.
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PMID:SerpinB2 mediated regulation of macrophage function during enteric infection. 2463 99

The antibacterial and anti-inflammatory activities, and protective effects of extracts (flavonoid glycosides) of Polygonum capitatum were investigated to detect the evidence for the utilization of the herb in the clinical therapy of gastritis caused by H. pylori. A mouse gastritis model was established using H. pylori. According to treating methods, model mice were random assigned into a model group (MG group), a triple antibiotics group (TG group, clarithromycin, omeprazole and amoxicillin), low/middle/high concentrations of flavonoid glycosides groups (LF, MF and HF groups) and low/middle/high concentrations of flavonoid glycosides and amoxicillin groups (LFA, MFA and HFA groups). A group with pathogen-free mice was regarded as a control group (CG group). The eradicate rates of H. pylori were 100%, 93%, 89% in TG, MFA and HF groups. The serum levels of IFN-gamma and gastrin were higher in a MG group than those from all other groups (P < 0.05). The serum levels of IFN-gamma and gastrin were reduced significantly in LF, MF and HF groups (P < 0.05) while little changes were observed in LFA, MFA and HFA groups. In contrast, the serum levels of IL-4 were lower and higher in MG and CG groups compared with other groups (P<0.05). The serum levels of IL-4 were increased significantly in LF, MF and HF groups (P < 0.05) while little changes were found in LFA, MFA and HFA groups. According to pathological scores, flavonoid glycosides therapy showed better protection for gastric injuries than the combination of flavonoid glycoside and amoxicillin (P < 0.05). The results suggested that flavonoid glycoside has repairing functions for gastric injuries. The results suggest that the plant can treat gastritis and protect against gastric injuries. The flavonoid glycosides from Polygonum capitatum should be developed as a potential drug for the therapy of gastritis caused by H. pylori.
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PMID:Flavonoid Glycosides of Polygonum capitatum Protect against Inflammation Associated with Helicobacter pylori Infection. 2599 58

Functional dyspepsia (FD) is one of the most prevalent functional gastrointestinal disorders, and more and more multicomponent drugs represented by traditional Chinese medicines have provided a favorable therapeutic effect in its treatment. However, their precise localization in the clinic, as well as corresponding mechanism, is ambiguous, thus hindering their widespread use. To meet this requirement, a precise and systematic approach based on a restriction of special disease-related molecules and the following network pharmacology analysis was developed and applied to a multicomponent conventional drug, XiaoErFuPi (XEFP) granules. Experimental verification of the results indicates that this approach can facilitate the prediction, and the precise and systematic efficacy of XEFP could be easily revealed, which shows that XEFP has an advantage over the positive control drug on lactate, gastrin, interleukin 4 and calcitonin gene-related peptide. Moreover, by the proteomics analysis, its superposition of multi-target effects was revealed and a new candidate target for the treatment of FD, striatin, was obtained and verified. This study provides a practicable precise approach for the investigation of the efficacy of multicomponent drugs against FD and offers a promising alternative for the systematical management of FD.
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PMID:Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia. 3134 Dec 40