Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing evidence suggests that interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes/macrophages, has various biological actions in addition to its immunological activities. In the present study, we examined the effect of IL-1 on gastric secretion and gastric ulcer formation in rats. Gastric secretion was assessed in conscious pylorus-ligated rats weighing approximately 200 g. The peripheral injection of IL-1 resulted in a dose-related inhibition of gastric acid output. The central injection of IL-1 similarly reduced gastric acid secretion at 100 times smaller doses than peripherally injected IL-1, suggesting that this gastric antisecretory action of IL-1 is mediated by the central nervous system. In addition, it was found that this inhibitory effect of IL-1, either peripherally or centrally administered, was still evident at 8 h after injection, indicating the long-lasting property of this IL-1 action. On the basis of these antisecretory actions of IL-1, we determined whether or not pretreatment with IL-1 would prevent experimentally induced gastric ulcer formation. As expected, the central administration of IL-1 dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion restraint stress, a well-established ulcerogenic procedure. These results clearly demonstrated that IL-1 has potent antisecretory and antiulcer effects that are mediated by the central nervous system. Moreover, these findings suggest that there may exist an "immune-brain-gut" axis, which is involved in the regulation of gastric secretion and mucosal homeostasis, especially under certain pathophysiological conditions that activate the immune system to release various cytokines including IL-1.
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PMID:Gastric antisecretory and antiulcer actions of interleukin-1. Evidence for the presence of an "immune-brain-gut" axis. 162 72

To evaluate the inflammatory changes during ulcer healing, we measured myeloperoxidase (MPO) activity and the inflammatory cytokine interleukin-8 (IL-8) in the gastric mucosa of 51 patients with gastric ulcers and 5 normal controls. MPO activity was measured by enzyme assay and IL-8 by ELISA, using biopsy samples taken from the ulcer margin and at 3 and 6 cm from the ulcer. Levels of MPO activity were significantly higher than in normal controls and peaked at the A2 (active) stage, and then gradually decreased and returned to basal levels at the S2 (scarring) stage. The area of increased MPO activity around the gastric ulcer was approximately 6 cm in diameter at the A2 stage, and this area decreased as the ulcer healed. IL-8 levels in gastric mucosa also increased significantly at the A2 stage, and the changes paralleled those of MPO activity during ulcer healing. MPO activity correlated well with the IL-8 level.
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PMID:The inflammatory reaction in mucosa during healing of gastric ulcers in humans. 877 95

According to the recent pharmacological findings, garlic is a preventive rather than therapeutic. Epidemiological studies in China, Italy and USA showed the inverse relationship between stomach and colon cancer incidences and dietary garlic intake. Anti-carcinogenic activities of garlic and its constituents including sulfides and S-allyl cysteine, have been demonstrated using several animal models. Garlic preparations has been also shown to lower serum cholesterol and triglyceride levels, which are major risk factors of cardiovascular diseases, through inhibition of their bio-synthesis in the liver, and to inhibit oxidation of low density lipoprotein. Furthermore, in vitro and in vivo studies have revealed that aged garlic extract stimulated immune functions, such as proliferation of lymphocyte, cytokine release, NK activity and phagocytosis. More recently, aged garlic extract has been demonstrated to prolong life span of senescence accelerated mice and prevent brain atrophy. Manufacturing processes significantly affect chemical constituents in garlic preparations. Different forms contain different phytochemicals and may have different effects and toxicities. For example, aged garlic extract inhibited t-BuOOH-induced oxidation, whereas raw garlic stimulated the oxidation. Although garlic has been used as a condiment and folklore for a long time, it has been noted to cause adverse reactions, such as stomach ulcer and anemia. Among the garlic preparations, only aged garlic extract has been proven to be safe through toxicological studies. Thus, aged garlic extract could be the most promising garlic preparation for disease prevention.
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PMID:[New pharmacological activities of garlic and its constituents]. 950 13

We investigated the relationship between microcirculatory disturbance and the host response to Helicobacter pylori infections in gastric ulcer scars to determine the role of endothelin-1 (ET) in ulcer recurrence. The subjects were divided into three groups. The GuS group consisted of patients who had red scarring (S1 stage) at the gastric angle with H. pylori, the gast+ group who had gastritis with H. pylori, and the gast- group who had gastritis without H. pylori. During endoscopic examination, biopsies were taken from the gastric angle. Mucosal ET, nitric oxide (NO), interleukin-8 (IL-8), and RANTES were measured. ET, inducible NO synthase (iNOS), and endothelial constitutive NOS (ecNOS) were immunostained. Mucosal ET and oxides of nitrogen (NOx) were significantly higher in the GuS group than in the other groups. IL-8 was elevated in the GuS and gast+ groups, and RANTES was elevated in the gast+ group (p < 0.01). There was prominent inflammatory cell infiltration in the GuS group. ET-positive cells were found in vascular smooth muscle, gastric epithelium, and gastric smooth muscle. iNOS-positive cells were found in vascular smooth muscle, gastric epithelium, gastric smooth muscle, and inflammatory cells. In conclusion, local inflammation and microcirculatory disturbance persist at the center of the ulcer scar (S1). Decreased cytokine levels and increased ET and NO (mainly synthesized by iNOS) levels suggested that microcirculatory disturbance is a more important factor than immune response in ulcer recurrence.
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PMID:Relationship between recurrence of gastric ulcer and the microcirculation. 959 26

We investigated the role of endogenous interleukin (IL)-1 in the mRNA expression of cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant (CINC)-1, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and transforming growth factor (TGF)-beta1 in acetic acid-induced gastric ulcers in rats. IL-1beta mRNA was not detected in the normal or intact mucosa of ulcerated stomachs, but its expression was induced in the ulcerated tissue. IL-1beta immunoreactivity was observed in macrophages/monocytes and fibroblasts in the ulcer base. COX-2, iNOS, and CINC-1 mRNAs were expressed by ulceration. EGF, bFGF, HGF, and TGF-beta1 mRNA expression was detected in the normal mucosa, and their levels were significantly elevated by ulceration. In contrast, COX-1 mRNA level did not differ between the normal and ulcerated tissues. In a culture of isolated ulcer bases, block of IL-1 with IL-1 receptor antagonist (IL-1RA) dose-dependently and significantly reduced the mRNA levels of COX-2, iNOS, CINC-1, HGF, and bFGF. In contrast, COX-1, EGF, and TGF-beta1 mRNA expression was not affected by IL-1RA. IL-1RA dose-dependently reduced prostaglandin E(2) production, total and iNOS activities, neutrophil chemotactic activity, and growth-promoting activity toward gastric epithelial cells in the ulcer base. Finally, the administration of IL-1RA caused a significant impairment of ulcer healing. These results indicate that IL-1, expressed in macrophages/monocytes and fibroblasts in the ulcer base, might up-regulate the mRNA expression of COX-2, iNOS, CINC-1, HGF, and bFGF, thereby contributing to gastric ulcer healing in rats.
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PMID:Regulation by endogenous interleukin-1 of mRNA expression of healing-related factors in gastric ulcers in rats. 1052 82

We investigated the role of nuclear factor-kappaB (NF-kappaB) in gastric ulcer healing in rats. NF-kappaB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-kappaB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1beta activated NF-kappaB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-kappaB action resulted in suppression of both their mRNA expression and increases in PGE(2) and CINC-1 levels induced by interleukin-1beta. Persistent prevention of NF-kappaB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1beta, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE(2) production were also reduced. These results demonstrate that NF-kappaB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.
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PMID:Role of nuclear factor-kappaB in gastric ulcer healing in rats. 1135 24

Infection of humans with Helicobacter pylori results in the development of chronic gastritis and plays an important role in gastric ulcer pathogenesis. Despite the infiltration of the mucosa with specific immunocompetent cells and production of specific antibodies, the infection usually persists for life. This study was performed to investigate if immunologic mechanisms exist which could contribute to the inability of the host to terminate the infection. Therefore, we compared the in vitro immunoreactivity of peripheral blood mononuclear cells (PBMC) from H. pylori-infected patients after stimulation with sonicated H. pylori bacteria from the stomach of the patient (autologous bacterial strain) with stimulation by bacteria from other patients (heterologous bacteria). We measured cell proliferation, expression of T cell activation markers CD25, HLA-DR, and CD71, as well as production ofinterleukin-10 (IL-10), an inhibitory cytokine. We found that the proliferative response of PBMC was significantly lower after autologous than after heterologous stimulation. Furthermore, secretion of IL-10 in the culture supernatants was significantly higher when PBMC were incubated with autologous than with heterologous H. pylori antigens. No significant differences between autologous or heterologous stimulation were observed in the increased expression of T cell activation markers. These data indicate that systemic immunologic response to H. pylori are strain-dependent. For further studies of the immune responses towards H. pylori, the use of an autologous stimulatory system seems necessary.
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PMID:Immune response to autologous and heterologous Helicobacter pylori antigens in humans. 1152 60

Since Marshall's discovery before 20 years, Helicobacter pylori (H. pylori) infection is reportedly to be associated with a variety of clinical outcomes including peptic ulcer disease and gastric cancer. The first step of the H. pylori colonization might be its adhesion to the surface epithelial cells, which evokes gastric inflammatory events initiated by neutrophil recruitment from the microcirculation. Mongolian gerbil is one of the suitable animal models for H. pylori infection, which exerts gastric ulcer and cancer with its bacterial infection. In H. pylori-colonized gerbils, extensive levels of microvascular leukocyte adhesion and migration into the parenchymal side and significant levels of inflammatory cell infiltration are encountered. Bacterial urease not only neutralizes gastric luminal acid, but also plays as an adhesion factor to the surface epithelium. Recently, such an adhesion to the epithelium is reported to be important for bacterial type IV secretory system, which intermediates Cag A injection into the epithelial cells. Then, multiple chemokine and cytokine networks are activated and mucosal inflammatory lesion formation would be completed. In the long-term colonization of H. pylori, gastric mucosal cell turnover would be modified due to persistent inflammation and then such deregulation of cell turnover might link to the precancerous lesion formation.
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PMID:Gastric mucosal response to Helicobacter pylori. 1252 36

This case control study presents data on the concentrations of nitrite and nitrate and a variety of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with gastritis, gastric ulcer and gastric cancer are studied and grouped according to infection by Helicobacter pylori. The 208 patients who underwent upper gastrointestinal endoscopic examination were classified as follows; H. pylori-positive gastritis (n = 32), H. pylori-negative gastritis (n = 32), H. pylori-positive ulcers (n = 34), H. pylori-negative ulcers (n = 34), 43 patients with H. pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy control individuals. Gastric fluids and blood samples were taken concomitantly. Cytokines and nitrite and nitrate determinations were attempted as soon as possible after collection of the samples. Nitrite and nitrate levels of serum and gastric fluids of H. pylori-positive gastritis and ulcers were higher than H. pylori-negative gastritis and ulcers. The concentrations of total nitrite and nitrate and cytokines (TNF-alpha, IL-2R, IL-6, and IL-8) in gastric fluids and sera of H. pylori-positive gastric cancer patients were higher than H. pylori-negative control groups. IL-1 beta level was significantly elevated in gastric fluid of infected cancer patients but not in serum. Taken together, the results suggest that an increase in cytokine-NO combination in gastric mucosa previously reported by many studies is not restricted to local infected gastric tissue but also detected in gastric fluid and sera of H. pylori-positive subjects and may have an important role in the pathogenesis and development of common gastric diseases.
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PMID:Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori. 1516 24

TNF-alpha has numerous biological activities, including the induction of chemokine expression, and is involved in many gastric injuries. C-C chemokines [monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha] and C-X-C chemokines [MIP-2 and cytokine-induced neutrophil chemoattractant (CINC)-2alpha] mediate chemotaxis of monocytes and neutrophils, respectively. We examined the roles of TNF-alpha and dynamics of chemokine expression in gastric ulceration including ulcer recurrence and indomethacin-induced injury. Rats with healed chronic gastric ulcers received intraperitoneal TNF-alpha to induce ulcer recurrence. Some rats were given neutralizing antibodies against neutrophils or MCP-1 together with TNF-alpha. In a separate experiment, rats were orally administered 20 mg/kg indomethacin with or without pretreatment with pentoxifylline (an inhibitor of TNF-alpha synthesis) or anti-MCP-1 antibody. TNF-alpha (1 microg/kg) induced gastric ulcer recurrence after 48 h, which was completely prevented by anti-neutrophil antibody. TNF-alpha increased the number of macrophages and MCP-1 mRNA expression in scarred mucosa from 4 h, whereas it increased MPO activities (marker of neutrophil infiltration) and mRNA expression of MIP-2 and CINC-2alpha from 24 h. Anti-MCP-1 antibody inhibited leukocyte infiltration with reduction of the levels of C-X-C chemokines and prevented ulcer recurrence. Indomethacin treatment increased TNF-alpha/chemokine mRNA expression from 30 min and induced macroscopic erosions after 4 h. Pentoxifylline inhibited the indomethacin-induced gastric injury with reduction of neutrophil infiltration and expression of chemokine (MCP-1, MIP-2, and CINC-2alpha). Anti-MCP-1 antibody also inhibited the injury and these inflammatory responses but did not affect TNF-alpha mRNA expression. In conclusion, increased MCP-1 triggered by TNF-alpha may play a key role in gastric ulceration by regulating leukocyte recruitment and chemokine expression.
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PMID:Monocyte chemotactic protein-1 regulates leukocyte recruitment during gastric ulcer recurrence induced by tumor necrosis factor-alpha. 1520 18


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